<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/NCT04505826</url>
  </required_header>
  <id_info>
    <org_study_id>OP-1250-001</org_study_id>
    <nct_id>NCT04505826</nct_id>
  </id_info>
  <brief_title>A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer</brief_title>
  <official_title>A Phase I Dose Escalation and Dose Expansion and Phase II Monotherapy Open-label, First-in-Human, Multicenter Study of OP-1250 in Adult Subjects With Advanced and/or Metastatic Hormone Receptor (HR)-Positive, HER2-negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Olema Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Olema Pharmaceuticals, Inc.</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>
      This clinical trial is a Phase I dose escalation and dose expansion and Phase II monotherapy&#xD;
      open-label, first-in-human, multicenter study of OP-1250 in adult subjects with advanced&#xD;
      and/or metastatic hormone receptor (HR)-positive, her2-negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I dose escalation and dose expansion and Phase II monotherapy open--label,&#xD;
      first--in--human study to determine the dose limiting toxicity (DLT), maximum tolerated dose&#xD;
      (MTD) and/or recommended Phase II dose (RP2D), to characterize the safety and pharmacokinetic&#xD;
      (PK) profile, and to estimate the preliminary anti-tumor activity of OP-1250 as a single&#xD;
      agent in adult subjects with hormone receptor (HR)-positive/human epidermal growth factor&#xD;
      receptor 2 (HER2)-negative metastatic or locally advanced breast cancer. This study comprises&#xD;
      2 Phases: Phase I (Part A [Dose Escalation] and Part B [Dose Expansion]) and Phase II.&#xD;
      Additionally, all subjects (Phase I and Phase II) will be eligible to participate in 1 of 2&#xD;
      sub-studies. Patients must have received at least 1 prior hormonal regimen and at least 6&#xD;
      months of a prior continuous endocrine therapy for locally advanced or metastatic disease.&#xD;
      Patients will be evaluated for treatment emergent adverse events (AEs) during study&#xD;
      participation, and toxicity will be assessed according to the National Cancer Institute (NCI)&#xD;
      Common Terminology Criteria for Adverse Events, Version 5.0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 13, 2020</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicities (DLT)</measure>
    <time_frame>The first 28 days of treatment</time_frame>
    <description>To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of OP-1250, the incidence of DLTs will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250</measure>
    <time_frame>Up to 42 days after end of treatment</time_frame>
    <description>Characterize the incidence, nature and severity of TEAEs and SAEs of OP-1250 according to NCI-CTCAE version 5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of OP-1250</measure>
    <time_frame>Every 28 days</time_frame>
    <description>Plasma concentrations of OP-1250 will be assessed at predefined intervals</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Anti-tumor activity of OP-1250</measure>
    <time_frame>Every 8 weeks</time_frame>
    <description>Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">153</enrollment>
  <condition>Hormone Receptor Positive Breast Carcinoma</condition>
  <condition>HER2-negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>OP-1250 Phase I Part A (Dose Escalation) and Part B (Dose Expansion)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase I Part A will evaluate the safety and pharmacokinetics (PK)of a range of OP-1250 doses to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Phase I Part B will evaluate the safety and PK of OP-1250 to confirm the RP2D dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OP-1250 Phase II</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This portion of the study further explores the clinical activity, safety, and PK of OP-1250 monotherapy at the RP2D and will estimate preliminary anti-tumor efficacy in 3 cohorts.&#xD;
Cohort A will enroll subjects with measurable disease without evidence of CNS metastases; Cohort B will enroll subjects with non-measurable (evaluable) disease without evidence of CNS metastases; and Cohort C will enroll subjects with evaluable disease (measurable and non-measurable) with CNS metastases.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OP-1250</intervention_name>
    <description>Complete Estrogen Receptor ANtagonist (CERAN)</description>
    <arm_group_label>OP-1250 Phase I Part A (Dose Escalation) and Part B (Dose Expansion)</arm_group_label>
    <arm_group_label>OP-1250 Phase II</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Must have received at least 1 prior hormonal regimen and at least 6 months of a prior&#xD;
             continuous endocrine therapy for locally advanced or metastatic disease&#xD;
&#xD;
          -  Must not have received prior oral endocrine therapy &lt; 2 weeks prior to first dose&#xD;
&#xD;
          -  Must not have received prior, chemotherapy in 2 weeks or within 5 half-lives whichever&#xD;
             is earlier, antibody therapy within 4 weeks or investigational therapy within 4 weeks&#xD;
             or 5 half-lives whichever is earlier, prior to the first dose&#xD;
&#xD;
          -  Adequate hepatic function&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Normal coagulation panel&#xD;
&#xD;
          -  Willingness to use effective contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Gastrointestinal disease&#xD;
&#xD;
          -  Significant renal disease&#xD;
&#xD;
          -  Significant cardiovascular disease&#xD;
&#xD;
          -  Significant ECG abnormalities&#xD;
&#xD;
          -  Ongoing systemic bacterial, fungal, or viral infection (requiring antimicrobial&#xD;
             therapy)&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Shilkrut, MD</last_name>
    <role>Study Director</role>
    <affiliation>Olema Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gurpreet Mathauda-Sahota, PharmD</last_name>
    <role>Study Director</role>
    <affiliation>Olema Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA Hematology/Oncology</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami, Sylvester Comprehensive Cancer Center</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advent Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Center</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute of Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Melvin and Bren Simon Comprehensive Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</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>Saint Luke's Hospital of Kansas City</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Taussig Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>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>Macquarie University</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2109</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICON Cancer Centre</name>
      <address>
        <city>Auchenflower</city>
        <state>Queensland</state>
        <zip>4066</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Research South Australia</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>August 20, 2023</last_update_submitted>
  <last_update_submitted_qc>August 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04505826
org study id: OP-1250-001
nct id: NCT04505826
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This clinical trial is a Phase I dose escalation and dose expansion and Phase II monotherapy
      open-label, first-in-human, multicenter study of OP-1250 in adult subjects with advanced
      and/or metastatic hormone receptor (HR)-positive, her2-negative breast cancer.
This is a Phase I dose escalation and dose expansion and Phase II monotherapy open--label,
      first--in--human study to determine the dose limiting toxicity (DLT), maximum tolerated dose
      (MTD) and/or recommended Phase II dose (RP2D), to characterize the safety and pharmacokinetic
      (PK) profile, and to estimate the preliminary anti-tumor activity of OP-1250 as a single
      agent in adult subjects with hormone receptor (HR)-positive/human epidermal growth factor
      receptor 2 (HER2)-negative metastatic or locally advanced breast cancer. This study comprises
      2 Phases: Phase I (Part A [Dose Escalation] and Part B [Dose Expansion]) and Phase II.
      Additionally, all subjects (Phase I and Phase II) will be eligible to participate in 1 of 2
      sub-studies. Patients must have received at least 1 prior hormonal regimen and at least 6
      months of a prior continuous endocrine therapy for locally advanced or metastatic disease.
      Patients will be evaluated for treatment emergent adverse events (AEs) during study
      participation, and toxicity will be assessed according to the National Cancer Institute (NCI)
      Common Terminology Criteria for Adverse Events, Version 5.0.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Limiting Toxicities (DLT)
time frame: The first 28 days of treatment
description: To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of OP-1250, the incidence of DLTs will be assessed.
measure: Characterize the incidence, nature and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) of OP-1250
time frame: Up to 42 days after end of treatment
description: Characterize the incidence, nature and severity of TEAEs and SAEs of OP-1250 according to NCI-CTCAE version 5.0
measure: Pharmacokinetics of OP-1250
time frame: Every 28 days
description: Plasma concentrations of OP-1250 will be assessed at predefined intervals
measure: Anti-tumor activity of OP-1250
time frame: Every 8 weeks
description: Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines
arm group label: OP-1250 Phase I Part A (Dose Escalation) and Part B (Dose Expansion)
arm group type: Experimental
description: Phase I Part A will evaluate the safety and pharmacokinetics (PK)of a range of OP-1250 doses to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Phase I Part B will evaluate the safety and PK of OP-1250 to confirm the RP2D dose.
arm group label: OP-1250 Phase II
arm group type: Experimental
description: This portion of the study further explores the clinical activity, safety, and PK of OP-1250 monotherapy at the RP2D and will estimate preliminary anti-tumor efficacy in 3 cohorts.
Cohort A will enroll subjects with measurable disease without evidence of CNS metastases; Cohort B will enroll subjects with non-measurable (evaluable) disease without evidence of CNS metastases; and Cohort C will enroll subjects with evaluable disease (measurable and non-measurable) with CNS metastases.
intervention type: Drug
intervention name: OP-1250
description: Complete Estrogen Receptor ANtagonist (CERAN)
arm group label: OP-1250 Phase I Part A (Dose Escalation) and Part B (Dose Expansion)
arm group label: OP-1250 Phase II
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Shilkrut, MD
role: Study Director
affiliation: Olema Pharmaceuticals, Inc.
last name: Gurpreet Mathauda-Sahota, PharmD
role: Study Director
affiliation: Olema Pharmaceuticals, Inc.
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country: Australia
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: No