<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02983604</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-350-1937</org_study_id>
    <secondary_id>2016-002365-63</secondary_id>
    <nct_id>NCT02983604</nct_id>
  </id_info>
  <brief_title>GS-5829 in Combination With Fulvestrant or Exemestane in Women With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer</brief_title>
  <official_title>A Phase 1b/2 Study of GS-5829 in Combination With Fulvestrant or Exemestane in Subjects With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objectives of the Phase 1b Dose Escalation part of this study are to characterize&#xD;
      the safety and tolerability of GS-5829 in combination with exemestane or fulvestrant and to&#xD;
      determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose of GS-5829 in&#xD;
      combination with fulvestrant in women with advanced estrogen receptor positive, HER2-negative&#xD;
      (ER+/HER2-) breast cancer.&#xD;
&#xD;
      The primary objective of the Randomized Phase 2 Dose Expansion portion of this study is to&#xD;
      evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant&#xD;
      alone in women with advanced ER+/HER2- breast cancer.&#xD;
&#xD;
      This study was terminated early and the Phase 2 portion of the study was not conducted.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">January 10, 2017</start_date>
  <completion_date type="Actual">July 19, 2018</completion_date>
  <primary_completion_date type="Actual">July 19, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>A DLT was a toxicity as defined below:&#xD;
Grade ≥ 4 neutropenia&#xD;
Grade ≥ 3 neutropenia with fever&#xD;
Grade ≥ 3 thrombocytopenia&#xD;
Grade ≥ 2 bleeding (e.g., gastrointestinal, respiratory, epistaxis, purpura)&#xD;
Grade ≥ 3 or higher non-hematologic toxicity, except:&#xD;
Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy&#xD;
Grade 3 diarrhea which persists for &lt; 72 hours in the absence of adequate medical therapy&#xD;
Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of the investigator is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk&#xD;
Treatment interruption of ≥ 7 days due to unresolved toxicity&#xD;
Grade 3 or Grade 4 elevation in aspartate transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Randomized Phase 2 Dose Expansion: Progression-Free Survival</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Progression-Free Survival (PFS) was defined as the interval from date of randomization to the earlier of the first documented confirmed disease progression or death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Days 1 and 15</time_frame>
    <description>Cmax is defined as the maximum observed concentration of drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829</measure>
    <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Day 15</time_frame>
    <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Randomized Phase 2 Dose Expansion: Overall Safety Profile as Assessed by the Percentage of Participants Experiencing Any Adverse Events (AEs), Grade 3 or 4 AEs, Treatment-Related AEs, or Abnormalities in Laboratory Tests or Electrocardiograms</measure>
    <time_frame>Baseline up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Randomized Phase 2 Dose Expansion: Overall Response Rate</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Overall response rate (ORR) was defined as the proportion of participants who achieve complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 study progression criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Randomized Phase 2 Dose Expansion: Clinical Benefit Rate</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Clinical benefit rate (CBR) was defined as the proportion of participants who achieve CR, PR, or stable disease that lasts for &gt; 24 weeks based on RECIST v. 1.1 study progression criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Randomized Phase 2 Dose Expansion: Overall Survival</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Overall survival was defined as the interval from date of randomization to date of death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Advanced Estrogen Receptor Positive HER2- Breast Cancer</condition>
  <arm_group>
    <arm_group_label>GS-5829 + exemestane (Phase 1b)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be sequentially enrolled at progressively higher dose levels of GS-5829 (up to 9 mg) in combination with exemestane and may continue with treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-5829 + fulvestrant (Phase 1b)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be sequentially enrolled at progressively higher dose levels of GS-5829 (up to 9 mg) in combination with fulvestrant and may continue with treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-5829 + fulvestrant (Phase 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive GS-5829 (dose determined from Phase 1b) + fulvestrant until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fulvestrant (Phase 2)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive fulvestrant alone until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GS-5829</intervention_name>
    <description>Tablet(s) administered orally once daily</description>
    <arm_group_label>GS-5829 + exemestane (Phase 1b)</arm_group_label>
    <arm_group_label>GS-5829 + fulvestrant (Phase 1b)</arm_group_label>
    <arm_group_label>GS-5829 + fulvestrant (Phase 2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exemestane</intervention_name>
    <description>25 mg tablet administered orally once daily (or in accordance with locally approved labeling)</description>
    <arm_group_label>GS-5829 + exemestane (Phase 1b)</arm_group_label>
    <other_name>Aromasin®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fulvestrant</intervention_name>
    <description>Administered every 28 days (± 3 days) intramuscularly in accordance with locally approved labeling&#xD;
Participants initiating fulvestrant on Cycle 1 Day 1 and have not received any prior dose of fulvestrant will receive a single additional dose of fulvestrant on Cycle 1 Day 15.</description>
    <arm_group_label>Fulvestrant (Phase 2)</arm_group_label>
    <arm_group_label>GS-5829 + fulvestrant (Phase 1b)</arm_group_label>
    <arm_group_label>GS-5829 + fulvestrant (Phase 2)</arm_group_label>
    <other_name>Faslodex®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed breast cancer with evidence of metastatic or&#xD;
             locally advanced disease not amenable to resection or radiation therapy with curative&#xD;
             intent and who have progressed during treatment with at least one prior hormonal&#xD;
             therapy&#xD;
&#xD;
               -  Phase 1b Dose Escalation - Individuals may have had unlimited prior hormonal&#xD;
                  therapy and a total of 2 prior chemotherapy regimens (adjuvant chemotherapy is&#xD;
                  considered 1 regimen). Individuals may have progressed on fulvestrant or&#xD;
                  exemestane.&#xD;
&#xD;
               -  Randomized Phase 2 Dose Expansion - Individuals may have disease progression&#xD;
                  during treatment or within 12 months of completion of endocrine therapy&#xD;
                  (tamoxifen, and/or AI) in the adjuvant setting, or disease progression during&#xD;
                  treatment with endocrine therapy (tamoxifen, AI or CDK4/6 inhibitor plus AI) for&#xD;
                  advanced/metastatic disease. Individuals may have had unlimited prior hormonal&#xD;
                  therapy, but must be naive to fulvestrant in the metastatic setting. A total of 2&#xD;
                  prior chemotherapies are allowed, however, only one for metastatic disease is&#xD;
                  permitted.&#xD;
&#xD;
          -  Documentation of ER positive (≥ 1% positive stained cells by local standards) based on&#xD;
             the most recent tumor biopsy, unless bone-only disease&#xD;
&#xD;
          -  Documented HER2-negative tumor based on local testing on most recent tumor biopsy&#xD;
             (immunohistochemistry score 0/1+ or negative by in situ hybridization HER2/CP17 ratio&#xD;
             &lt; 2 or for single probe assessment HER2 copy number &lt; 4)&#xD;
&#xD;
          -  Post-, pre- or peri-menopausal women considered to be in the post-menopausal state as&#xD;
             defined by one of the following:&#xD;
&#xD;
               -  Age ≥ 60 years&#xD;
&#xD;
               -  Age &lt; 60 years and cessation of regular menses for at least 12 consecutive months&#xD;
                  in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and&#xD;
                  serum estradiol and follicle-stimulating hormone (FSH) level within the&#xD;
                  post-menopausal range&#xD;
&#xD;
               -  Prior bilateral oophorectomy&#xD;
&#xD;
               -  Pre-/peri-menopausal women can be enrolled if amenable to be treated with the&#xD;
                  luteinizing-hormone releasing hormone (LHRH) agonist, goserelin. Individuals must&#xD;
                  have commenced treatment with goserelin or an alternative LHRH agonist at least 4&#xD;
                  weeks prior to Cycle 1 Day 1 (C1D1). If individuals have received an alternative&#xD;
                  LHRH agonist prior to study entry, they must switch to goserelin on or before&#xD;
                  Cycle 1 Day 1 (C1D1) for the duration of the study&#xD;
&#xD;
          -  Measurable disease defined per RECIST v. 1.1, or bone-only disease must have a lytic&#xD;
             or mixed lytic blastic lesion that can be accurately assessed by computed tomography&#xD;
             (CT) or magnetic resonance imaging (MRI). Individuals with bone-only disease and&#xD;
             blastic-only metastases are not eligible&#xD;
&#xD;
          -  All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before&#xD;
             the start of study drug dosing (with the exception of alopecia [Grade 1 or 2&#xD;
             permitted] and neurotoxicity [Grade 1 or 2 permitted])&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1&#xD;
&#xD;
          -  Life expectancy of ≥ 3 months, in the opinion of the investigator&#xD;
&#xD;
          -  Adequate organ function defined as follows:&#xD;
&#xD;
               -  Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil&#xD;
                  count (ANC) ≥ 1.5 x 10^9/L (without platelet transfusion or any granulocytic&#xD;
                  growth factors within previous 7 days of the hematologic laboratory values&#xD;
                  obtained at screening visit)&#xD;
&#xD;
               -  Hepatic: aspartate transaminase (AST) / alanine transaminase (ALT) ≤ 2.5 x upper&#xD;
                  limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); total or&#xD;
                  conjugated bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               -  Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min as&#xD;
                  calculated by the Cockroft-Gault method&#xD;
&#xD;
          -  Coagulation: International Normalized Ratio (INR) ≤ 1.2&#xD;
&#xD;
          -  Negative serum pregnancy test&#xD;
&#xD;
          -  Females of childbearing potential who engage in heterosexual intercourse must agree to&#xD;
             use protocol specified method(s) of contraception as described in the study protocol&#xD;
&#xD;
          -  Females who are nursing must agree to discontinue nursing before the first dose of&#xD;
             GS-5829&#xD;
&#xD;
          -  Able and willing to provide written informed consent to participate in the study&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  History or evidence of clinically significant disorder, condition, or disease that, in&#xD;
             the opinion of the investigator or the Gilead medical monitor would pose a risk to&#xD;
             individual safety or interfere with the study evaluations, procedures, or completion&#xD;
&#xD;
          -  Known brain metastasis or leptomeningeal disease (Note: if treated and stable at least&#xD;
             6 months prior to enrollment, individual is eligible).&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, active uncontrolled&#xD;
             infection, active or chronic bleeding event within 28 days prior to C1D1, uncontrolled&#xD;
             cardiac arrhythmia, or psychiatric illness/social situation that would limit&#xD;
             compliance with study requirements as judged by treating physician&#xD;
&#xD;
          -  Myocardial infarction, symptomatic congestive heart failure (New York Heart&#xD;
             Association Classification &gt; Class II), unstable angina, or serious uncontrolled&#xD;
             cardiac arrhythmia within the last 6 months of C1D1&#xD;
&#xD;
          -  Major surgery, defined as any surgical procedure that involves general anesthesia and&#xD;
             a significant incision (i.e., larger than what is required for placement of central&#xD;
             venous access, percutaneous feeding tube) within 28 days of C1D1&#xD;
&#xD;
          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly&#xD;
             alter the absorption of GS-5829, including any unresolved nausea, vomiting, or&#xD;
             diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) Grade &gt; 1&#xD;
&#xD;
          -  Minor surgical procedure(s) within 7 days of enrollment or randomization, or not yet&#xD;
             recovered from prior surgery (placement of central venous access device, fine needle&#xD;
             aspiration, or endoscopic biliary stent ≥ 1 day before enrollment or randomization is&#xD;
             acceptable)&#xD;
&#xD;
          -  History of a concurrent or second malignancy, except for: adequately treated local&#xD;
             basal cell or squamous cell carcinoma of the skin; cervical carcinoma in situ;&#xD;
             superficial bladder cancer; adequately treated Stage 1 or 2 cancer currently in&#xD;
             complete remission; any other cancer that has been in complete remission for ≥ 5 years&#xD;
&#xD;
          -  Anti-tumor therapy (chemotherapy, chemoradiation, radiation, antibody therapy,&#xD;
             molecular targeted therapy) within 21 days or 5 half-lives whichever is longer, of&#xD;
             C1D1 (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t1/2 &gt; 10 days);&#xD;
             5 half-lives of any investigational drug; concurrent use of goserelin for&#xD;
             pre-/peri-menopausal breast cancer and exemestane or fulvestrant per the protocol are&#xD;
             permitted&#xD;
&#xD;
          -  History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia&#xD;
             method) at screening is prolonged (&gt; 470 ms). Individuals who screen fail due to this&#xD;
             criterion are not eligible to be re-screened&#xD;
&#xD;
          -  Prior exposure to any bromodomain (BET) inhibitors&#xD;
&#xD;
          -  Known hypersensitivity to the study drugs (GS 5829, fulvestrant or exemestane), the&#xD;
             metabolites, or formulation excipients&#xD;
&#xD;
          -  Immunotherapy within 6 months of C1D1&#xD;
&#xD;
          -  Evidence of bleeding diathesis or clinically significant bleeding, within 28 days of&#xD;
             C1D1 or history of hemoptysis of &gt; 2.5 mL/1 teaspoon within 6 months of C1D1&#xD;
&#xD;
          -  Anticoagulation/antiplatelet therapy within 7 days of C1D1, including acetylsalicylic&#xD;
             acid, low molecular weight heparin, or warfarin&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Hepatitis B surface Antigen (HBsAg) positive&#xD;
&#xD;
          -  Hepatitis C virus (HCV) antibody positive with HCV RNA positive&#xD;
&#xD;
          -  Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or moderate/strong CYP3A4&#xD;
             inducers within 2 weeks prior to C1D1&#xD;
&#xD;
          -  History of high grade esophageal or gastric varices&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford Women's Cancer Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allina Health, Virginia Piper Cancer Institute</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University Medical Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology Associates, PS (dba Summit Cancer Centers)</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <results_first_submitted>July 15, 2019</results_first_submitted>
  <results_first_submitted_qc>July 15, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 7, 2019</results_first_posted>
  <last_update_submitted>July 15, 2019</last_update_submitted>
  <last_update_submitted_qc>July 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Exemestane</keyword>
  <keyword>Aromasin</keyword>
  <keyword>Fulvestrant</keyword>
  <keyword>Faslodex</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>HER 2-</keyword>
  <keyword>Estrogen receptor positive</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fulvestrant</mesh_term>
    <mesh_term>Exemestane</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol: Original</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 17, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02983604/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Amendment 1</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 10, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02983604/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Amendment 2</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02983604/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02983604/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at study sites in the United States. The first participant was screened on 10 January 2017. The last study visit occurred on 19 July 2018.</recruitment_details>
      <pre_assignment_details>17 participants were screened.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>GS-5829 4 mg + Exemestane</title>
          <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
        </group>
        <group group_id="P2">
          <title>GS-5829 4 mg + Fulvestrant</title>
          <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
        <group group_id="P3">
          <title>GS-5829 6 mg + Fulvestrant</title>
          <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
        <group group_id="P4">
          <title>GS-5829 9 mg + Fulvestrant</title>
          <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Enrolled but not Treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>GS-5829 4 mg + Exemestane</title>
          <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
        </group>
        <group group_id="B2">
          <title>GS-5829 4 mg + Fulvestrant</title>
          <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
        <group group_id="B3">
          <title>GS-5829 6 mg + Fulvestrant</title>
          <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
        <group group_id="B4">
          <title>GS-5829 9 mg + Fulvestrant</title>
          <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="13"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.3" spread="4.50"/>
                    <measurement group_id="B2" value="61.3" spread="7.51"/>
                    <measurement group_id="B3" value="63.0" spread="9.54"/>
                    <measurement group_id="B4" value="65.0" spread="12.29"/>
                    <measurement group_id="B5" value="61.9" spread="7.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829</title>
        <description>A DLT was a toxicity as defined below:&#xD;
Grade ≥ 4 neutropenia&#xD;
Grade ≥ 3 neutropenia with fever&#xD;
Grade ≥ 3 thrombocytopenia&#xD;
Grade ≥ 2 bleeding (e.g., gastrointestinal, respiratory, epistaxis, purpura)&#xD;
Grade ≥ 3 or higher non-hematologic toxicity, except:&#xD;
Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy&#xD;
Grade 3 diarrhea which persists for &lt; 72 hours in the absence of adequate medical therapy&#xD;
Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of the investigator is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk&#xD;
Treatment interruption of ≥ 7 days due to unresolved toxicity&#xD;
Grade 3 or Grade 4 elevation in aspartate transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug</description>
        <time_frame>Baseline up to 28 days</time_frame>
        <population>The DLT Analysis Set included all participants in the Safety Analysis Set who completed all treatment and safety procedures through Day 28, inclusive, or experienced a DLT prior to Day 28, exclusive.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829</title>
          <description>A DLT was a toxicity as defined below:&#xD;
Grade ≥ 4 neutropenia&#xD;
Grade ≥ 3 neutropenia with fever&#xD;
Grade ≥ 3 thrombocytopenia&#xD;
Grade ≥ 2 bleeding (e.g., gastrointestinal, respiratory, epistaxis, purpura)&#xD;
Grade ≥ 3 or higher non-hematologic toxicity, except:&#xD;
Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy&#xD;
Grade 3 diarrhea which persists for &lt; 72 hours in the absence of adequate medical therapy&#xD;
Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of the investigator is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk&#xD;
Treatment interruption of ≥ 7 days due to unresolved toxicity&#xD;
Grade 3 or Grade 4 elevation in aspartate transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug</description>
          <population>The DLT Analysis Set included all participants in the Safety Analysis Set who completed all treatment and safety procedures through Day 28, inclusive, or experienced a DLT prior to Day 28, exclusive.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Randomized Phase 2 Dose Expansion: Progression-Free Survival</title>
        <description>Progression-Free Survival (PFS) was defined as the interval from date of randomization to the earlier of the first documented confirmed disease progression or death from any cause.</description>
        <time_frame>Baseline up to 2 years</time_frame>
        <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Randomized Phase 2 Dose Expansion: Progression-Free Survival</title>
          <description>Progression-Free Survival (PFS) was defined as the interval from date of randomization to the earlier of the first documented confirmed disease progression or death from any cause.</description>
          <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829</title>
        <description>Cmax is defined as the maximum observed concentration of drug.</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Days 1 and 15</time_frame>
        <population>The PK Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 nonmissing postdose concentration value reported by the PK laboratory, excluding participants who received concomitant medications prohibited in this study. Only participants with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829</title>
          <description>Cmax is defined as the maximum observed concentration of drug.</description>
          <population>The PK Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 nonmissing postdose concentration value reported by the PK laboratory, excluding participants who received concomitant medications prohibited in this study. Only participants with available data were analyzed.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="318.25" spread="107.844"/>
                    <measurement group_id="O2" value="247.00" spread="3.464"/>
                    <measurement group_id="O3" value="244.00" spread="9.000"/>
                    <measurement group_id="O4" value="518.00" spread="60.811"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="389.666" spread="105.6424"/>
                    <measurement group_id="O2" value="370.333" spread="52.5483"/>
                    <measurement group_id="O3" value="375.666" spread="67.0919"/>
                    <measurement group_id="O4" value="634.000" spread="46.6690"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829</title>
        <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
        <time_frame>Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Day 15</time_frame>
        <population>Participants in the PK Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829</title>
          <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
          <population>Participants in the PK Analysis Set with available data were analyzed.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4989.809" spread="1655.8737"/>
                    <measurement group_id="O2" value="5218.820" spread="1326.2407"/>
                    <measurement group_id="O3" value="3937.709" spread="667.4396"/>
                    <measurement group_id="O4" value="7638.847" spread="938.3444"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Randomized Phase 2 Dose Expansion: Overall Safety Profile as Assessed by the Percentage of Participants Experiencing Any Adverse Events (AEs), Grade 3 or 4 AEs, Treatment-Related AEs, or Abnormalities in Laboratory Tests or Electrocardiograms</title>
        <time_frame>Baseline up to 2 years</time_frame>
        <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Randomized Phase 2 Dose Expansion: Overall Safety Profile as Assessed by the Percentage of Participants Experiencing Any Adverse Events (AEs), Grade 3 or 4 AEs, Treatment-Related AEs, or Abnormalities in Laboratory Tests or Electrocardiograms</title>
          <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Randomized Phase 2 Dose Expansion: Overall Response Rate</title>
        <description>Overall response rate (ORR) was defined as the proportion of participants who achieve complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 study progression criteria.</description>
        <time_frame>Baseline up to 2 years</time_frame>
        <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Randomized Phase 2 Dose Expansion: Overall Response Rate</title>
          <description>Overall response rate (ORR) was defined as the proportion of participants who achieve complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 study progression criteria.</description>
          <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Randomized Phase 2 Dose Expansion: Clinical Benefit Rate</title>
        <description>Clinical benefit rate (CBR) was defined as the proportion of participants who achieve CR, PR, or stable disease that lasts for &gt; 24 weeks based on RECIST v. 1.1 study progression criteria.</description>
        <time_frame>Baseline up to 2 years</time_frame>
        <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Randomized Phase 2 Dose Expansion: Clinical Benefit Rate</title>
          <description>Clinical benefit rate (CBR) was defined as the proportion of participants who achieve CR, PR, or stable disease that lasts for &gt; 24 weeks based on RECIST v. 1.1 study progression criteria.</description>
          <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Randomized Phase 2 Dose Expansion: Overall Survival</title>
        <description>Overall survival was defined as the interval from date of randomization to date of death from any cause.</description>
        <time_frame>Baseline up to 2 years</time_frame>
        <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>GS-5829 4 mg + Exemestane</title>
            <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
          </group>
          <group group_id="O2">
            <title>GS-5829 4 mg + Fulvestrant</title>
            <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O3">
            <title>GS-5829 6 mg + Fulvestrant</title>
            <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
          <group group_id="O4">
            <title>GS-5829 9 mg + Fulvestrant</title>
            <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)</description>
          </group>
        </group_list>
        <measure>
          <title>Randomized Phase 2 Dose Expansion: Overall Survival</title>
          <description>Overall survival was defined as the interval from date of randomization to date of death from any cause.</description>
          <population>As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days</time_frame>
      <desc>Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>GS-5829 4 mg + Exemestane</title>
          <description>GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily</description>
        </group>
        <group group_id="E2">
          <title>GS-5829 4 mg + Fulvestrant</title>
          <description>GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
        <group group_id="E3">
          <title>GS-5829 6 mg + Fulvestrant</title>
          <description>GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
        <group group_id="E4">
          <title>GS-5829 9 mg + Fulvestrant</title>
          <description>GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Abdominal tenderness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Irritable bowel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Fungal skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Musculoskeletal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastases to central nervous system</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:&#xD;
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or&#xD;
The study has been completed at all study sites for at least 2 years</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gilead Clinical Study Information Center</name_or_title>
      <organization>Gilead Sciences</organization>
      <phone>1-833-445-3230 (GILEAD-0)</phone>
      <email>GileadClinicalTrials@gilead.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02983604
org study id: GS-US-350-1937
secondary id: 2016-002365-63
nct id: NCT02983604
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objectives of the Phase 1b Dose Escalation part of this study are to characterize
      the safety and tolerability of GS-5829 in combination with exemestane or fulvestrant and to
      determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose of GS-5829 in
      combination with fulvestrant in women with advanced estrogen receptor positive, HER2-negative
      (ER+/HER2-) breast cancer.

      The primary objective of the Randomized Phase 2 Dose Expansion portion of this study is to
      evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant
      alone in women with advanced ER+/HER2- breast cancer.

      This study was terminated early and the Phase 2 portion of the study was not conducted.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829
time frame: Baseline up to 28 days
description: A DLT was a toxicity as defined below:
Grade ≥ 4 neutropenia
Grade ≥ 3 neutropenia with fever
Grade ≥ 3 thrombocytopenia
Grade ≥ 2 bleeding (e.g., gastrointestinal, respiratory, epistaxis, purpura)
Grade ≥ 3 or higher non-hematologic toxicity, except:
Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy
Grade 3 diarrhea which persists for < 72 hours in the absence of adequate medical therapy
Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of the investigator is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk
Treatment interruption of ≥ 7 days due to unresolved toxicity
Grade 3 or Grade 4 elevation in aspartate transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug
measure: Randomized Phase 2 Dose Expansion: Progression-Free Survival
time frame: Baseline up to 2 years
description: Progression-Free Survival (PFS) was defined as the interval from date of randomization to the earlier of the first documented confirmed disease progression or death from any cause.
measure: Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Days 1 and 15
description: Cmax is defined as the maximum observed concentration of drug.
measure: Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829
time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Day 15
description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
measure: Randomized Phase 2 Dose Expansion: Overall Safety Profile as Assessed by the Percentage of Participants Experiencing Any Adverse Events (AEs), Grade 3 or 4 AEs, Treatment-Related AEs, or Abnormalities in Laboratory Tests or Electrocardiograms
time frame: Baseline up to 2 years
measure: Randomized Phase 2 Dose Expansion: Overall Response Rate
time frame: Baseline up to 2 years
description: Overall response rate (ORR) was defined as the proportion of participants who achieve complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 study progression criteria.
measure: Randomized Phase 2 Dose Expansion: Clinical Benefit Rate
time frame: Baseline up to 2 years
description: Clinical benefit rate (CBR) was defined as the proportion of participants who achieve CR, PR, or stable disease that lasts for > 24 weeks based on RECIST v. 1.1 study progression criteria.
measure: Randomized Phase 2 Dose Expansion: Overall Survival
time frame: Baseline up to 2 years
description: Overall survival was defined as the interval from date of randomization to date of death from any cause.
arm group label: GS-5829 + exemestane (Phase 1b)
arm group type: Experimental
description: Participants will be sequentially enrolled at progressively higher dose levels of GS-5829 (up to 9 mg) in combination with exemestane and may continue with treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.
arm group label: GS-5829 + fulvestrant (Phase 1b)
arm group type: Experimental
description: Participants will be sequentially enrolled at progressively higher dose levels of GS-5829 (up to 9 mg) in combination with fulvestrant and may continue with treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.
arm group label: GS-5829 + fulvestrant (Phase 2)
arm group type: Experimental
description: Participants will receive GS-5829 (dose determined from Phase 1b) + fulvestrant until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.
arm group label: Fulvestrant (Phase 2)
arm group type: Active Comparator
description: Participants will receive fulvestrant alone until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.
intervention type: Drug
intervention name: GS-5829
description: Tablet(s) administered orally once daily
arm group label: GS-5829 + exemestane (Phase 1b)
arm group label: GS-5829 + fulvestrant (Phase 1b)
arm group label: GS-5829 + fulvestrant (Phase 2)
intervention type: Drug
intervention name: Exemestane
description: 25 mg tablet administered orally once daily (or in accordance with locally approved labeling)
arm group label: GS-5829 + exemestane (Phase 1b)
other name: Aromasin®
intervention type: Drug
intervention name: Fulvestrant
description: Administered every 28 days (± 3 days) intramuscularly in accordance with locally approved labeling
Participants initiating fulvestrant on Cycle 1 Day 1 and have not received any prior dose of fulvestrant will receive a single additional dose of fulvestrant on Cycle 1 Day 15.
arm group label: Fulvestrant (Phase 2)
arm group label: GS-5829 + fulvestrant (Phase 1b)
arm group label: GS-5829 + fulvestrant (Phase 2)
other name: Faslodex®
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Fulvestrant
mesh term: Exemestane
provided document: 
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 