<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/NCT03257722</url>
  </required_header>
  <id_info>
    <org_study_id>GCC-16053</org_study_id>
    <nct_id>NCT03257722</nct_id>
  </id_info>
  <brief_title>Pembrolizumab + Idelalisib for Lung Cancer Study</brief_title>
  <acronym>PIL</acronym>
  <official_title>A Phase Ib /II Trial of Pembrolizumab and Idelalisib in Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Failed Immune Checkpoint Inhibitor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhonglin Hao</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Augusta University</source>
  <oversight_info>
    <has_dmc>Yes</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 is a phase 1b/2 study to determine the safety and effectiveness of the combination of&#xD;
      pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune&#xD;
      therapy. This study is being done to see if adding another immune modulator (idelalisib) to&#xD;
      standard pembrolizumab will increase response rates, compared to the response seen with&#xD;
      pembrolizumab alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1b/2 study to determine the safety and effectiveness of the combination of&#xD;
      pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune&#xD;
      therapy. Pembrolizumab is an anti-PD-1 immunotherapy that is given intravenously and is&#xD;
      approved for treatment of malignant NSCLC. Idelalisib is the first-in-class oral PI3K-δ&#xD;
      inhibitor that is approved for treatment of certain forms of leukemia and lymphoma.&#xD;
&#xD;
      Immune checkpoint inhibitors (such as anti-PD-1) are effective in treating NSCLC as a single&#xD;
      agent, but overall response isn't optimal; overall response rates (ORR) are only ~20% on&#xD;
      average. The goal of this study is to see whether combining standard therapy with additional&#xD;
      immune modulators will increase response rates, compared to the response seen with&#xD;
      pembrolizumab monotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Anticipated">August 2021</completion_date>
  <primary_completion_date type="Anticipated">August 2020</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>
    <intervention_model_description>This is an open labeled, single arm, interventional study combining standard pembrolizumab (MK-3475, trade name: Keytruda) with investigational agent, idelalisib (trade name: Zydelig) in non-small cell lung cancer (NSCLC). The study will enroll patients in two phases: a dose finding/tolerability assessment phase and an efficacy assessment phase.&#xD;
The Phase 1b (modified 3+3 dose escalation) assessment will determine the safe dose of idelalisib in combination with pembrolizumab that down-regulates the activity of T-regulatory function (Treg).&#xD;
The Phase 2 efficacy assessment will enroll patients to detect whether idelalisib added to pembrolizumab at the phase 2 recommended dose (P2RD) will result in further objective response.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03</measure>
    <time_frame>First 9 weeks at each dose level</time_frame>
    <description>Modified 3+3 dose escalation design will be used to determine whether the addition of idelalisib to standard pembrolizumab is safe and tolerable in checkpoint inhibitor refractory NSCLC patients. An initial cohort of 3 patients will receive 50 mg twice daily idelalisib with standard pembrolizumab. If none of the 3 patients develop a DLT, another 3 patients will be enrolled. Dose will be escalated or de-escalated based on the occurrence of DLTs. All events will be assessed for possible, probable, or definite relation to idelalisib.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dose-Finding Assessment for optimum dose of idelalisib in combination with pembrolizumab</measure>
    <time_frame>18-27 weeks</time_frame>
    <description>Determine the phase 2 recommended dose (P2RD) of idelalisib, in combination with pembrolizumab, in patients with checkpoint inhibitor refractory NSCLC. If no more than 1/6 patients in initial cohort develop a DLT, the patients will be tested for T-regulatory cell function suppression (80% suppression in 80% of patients). If dose is escalated or de-escalated, testing will continue to assess for optimal T-reg suppression. The dose at which the tolerability and suppression criteria are both met will be declared the P2RD and the study will proceed to phase 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rates (ORR) to combination therapy</measure>
    <time_frame>18 weeks - 2 years</time_frame>
    <description>To determine whether addition of idelalisib to pembrolizumab in NSCLC improves ORR over that seen with pembrolizumab or other immune checkpoint inhibitors alone in treatment of NSCLC.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Metastasis</condition>
  <condition>Recurrence</condition>
  <arm_group>
    <arm_group_label>Phase 1 Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sequential cohorts of 3 patients will receive pembrolizumab 200 mg intravenously every 3 weeks, in addition to the oral drug, idelalisib, every day for 21 days. The first group of 3 will receive idelalisib 50 mg twice daily; the next cohort will receive idelalisib 100 mg twice daily; the last cohort will receive idelalisib 150 mg twice daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 Efficacy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients in the efficacy assessment phase will be treated with pembrolizumab (200 mg intravenously every 3 weeks) in combination with oral idelalisib (dose not exceeding 150 mg twice daily, per the phase 1 assessment) for 18 weeks before maintenance with pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, until disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Anti PD-1 immunotherapeutic agent, which blocks a protective mechanism on cancer cells to allow the immune system to destroy cancer cells. Administered intravenously (IV).</description>
    <arm_group_label>Phase 1 Dose Escalation</arm_group_label>
    <arm_group_label>Phase 2 Efficacy</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>MK-3475</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Idelalisib</intervention_name>
    <description>Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO).</description>
    <arm_group_label>Phase 1 Dose Escalation</arm_group_label>
    <arm_group_label>Phase 2 Efficacy</arm_group_label>
    <other_name>Zydelig</other_name>
    <other_name>GS-1101</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        All subjects must have documented metastatic or recurrent NSCLC from biopsy. They must have&#xD;
        failed or progressed on platinum-based chemotherapy (e.g. cisplatin, carboplatin) as well&#xD;
        as immune checkpoint inhibitor therapy (e.g nivolumab or pembrolizumab). Patients with&#xD;
        EGFR/ALK mutations/translocations must have failed or progressed on small molecule&#xD;
        inhibitor therapies (e.g. erlotinib, afatinib, etc.).&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Have at least one measurable lesion&#xD;
&#xD;
          -  Have an ECOG Performance Status of 1 or less&#xD;
&#xD;
          -  Demonstrate adequate organ function as defined in the protocol.&#xD;
&#xD;
          -  Female subjects of childbearing potential must have a negative pregnancy test before&#xD;
             starting treatment; they must also be willing to use two methods of birth control or&#xD;
             abstain from heterosexual activity for the duration of the study.&#xD;
&#xD;
          -  Male subjects must agree to use an adequate method of contraception starting with the&#xD;
             first dose of study therapy through the duration of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently receiving study drug in another trial; or has participated in an&#xD;
             investigational drug study within 3 weeks of the first dose of treatment.&#xD;
&#xD;
          -  Is within 3 weeks of most recent chemotherapy.&#xD;
&#xD;
          -  Has a history of hypersensitivity to pembrolizumab or idelalisib, or any of their&#xD;
             excipients.&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Subjects with previously treated, stable, brain metastases may&#xD;
             participate; carcinomatous meningitis is excluded regardless of clinical stability.&#xD;
&#xD;
          -  Has known history of non-infectious pneumonitis that required steroid use or has&#xD;
             current pneumonitis.&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis)&#xD;
&#xD;
          -  Has active autoimmune disease that has required treatment; known history of Human&#xD;
             Immunodeficiency Virus (HIV); known active Hepatitis B or Hepatitis C.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial&#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>Zhonglin Hao, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Georgia Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lisa Marshall, MSN, RN, CNL</last_name>
    <phone>706-721-5095</phone>
    <email>LMarshall@augusta.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carrie McAteer, BA, CCRC</last_name>
    <phone>706-721-1409</phone>
    <email>Cancer_Center_Trials@augusta.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Georgia Cancer Center at Augusta University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>September 27, 2017</last_update_submitted>
  <last_update_submitted_qc>September 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Augusta University</investigator_affiliation>
    <investigator_full_name>Zhonglin Hao</investigator_full_name>
    <investigator_title>Associate Professor of Medicine, Cancer Biology; Leader, Thoracic Oncology Program, Georgia Cancer Center</investigator_title>
  </responsible_party>
  <keyword>Non Small Cell Lung Cancer</keyword>
  <keyword>Metastasis</keyword>
  <keyword>Recurrence</keyword>
  <keyword>Immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Idelalisib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 3, 2023</submitted>
    <returned>August 25, 2023</returned>
  </pending_results>
  <!-- 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/NCT03257722
org study id: GCC-16053
nct id: NCT03257722
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 1b/2 study to determine the safety and effectiveness of the combination of
      pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune
      therapy. This study is being done to see if adding another immune modulator (idelalisib) to
      standard pembrolizumab will increase response rates, compared to the response seen with
      pembrolizumab alone.
This is a phase 1b/2 study to determine the safety and effectiveness of the combination of
      pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune
      therapy. Pembrolizumab is an anti-PD-1 immunotherapy that is given intravenously and is
      approved for treatment of malignant NSCLC. Idelalisib is the first-in-class oral PI3K-δ
      inhibitor that is approved for treatment of certain forms of leukemia and lymphoma.

      Immune checkpoint inhibitors (such as anti-PD-1) are effective in treating NSCLC as a single
      agent, but overall response isn't optimal; overall response rates (ORR) are only ~20% on
      average. The goal of this study is to see whether combining standard therapy with additional
      immune modulators will increase response rates, compared to the response seen with
      pembrolizumab monotherapy.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: This is an open labeled, single arm, interventional study combining standard pembrolizumab (MK-3475, trade name: Keytruda) with investigational agent, idelalisib (trade name: Zydelig) in non-small cell lung cancer (NSCLC). The study will enroll patients in two phases: a dose finding/tolerability assessment phase and an efficacy assessment phase.
The Phase 1b (modified 3+3 dose escalation) assessment will determine the safe dose of idelalisib in combination with pembrolizumab that down-regulates the activity of T-regulatory function (Treg).
The Phase 2 efficacy assessment will enroll patients to detect whether idelalisib added to pembrolizumab at the phase 2 recommended dose (P2RD) will result in further objective response.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03
time frame: First 9 weeks at each dose level
description: Modified 3+3 dose escalation design will be used to determine whether the addition of idelalisib to standard pembrolizumab is safe and tolerable in checkpoint inhibitor refractory NSCLC patients. An initial cohort of 3 patients will receive 50 mg twice daily idelalisib with standard pembrolizumab. If none of the 3 patients develop a DLT, another 3 patients will be enrolled. Dose will be escalated or de-escalated based on the occurrence of DLTs. All events will be assessed for possible, probable, or definite relation to idelalisib.
measure: Dose-Finding Assessment for optimum dose of idelalisib in combination with pembrolizumab
time frame: 18-27 weeks
description: Determine the phase 2 recommended dose (P2RD) of idelalisib, in combination with pembrolizumab, in patients with checkpoint inhibitor refractory NSCLC. If no more than 1/6 patients in initial cohort develop a DLT, the patients will be tested for T-regulatory cell function suppression (80% suppression in 80% of patients). If dose is escalated or de-escalated, testing will continue to assess for optimal T-reg suppression. The dose at which the tolerability and suppression criteria are both met will be declared the P2RD and the study will proceed to phase 2.
measure: Overall Response Rates (ORR) to combination therapy
time frame: 18 weeks - 2 years
description: To determine whether addition of idelalisib to pembrolizumab in NSCLC improves ORR over that seen with pembrolizumab or other immune checkpoint inhibitors alone in treatment of NSCLC.
arm group label: Phase 1 Dose Escalation
arm group type: Experimental
description: Sequential cohorts of 3 patients will receive pembrolizumab 200 mg intravenously every 3 weeks, in addition to the oral drug, idelalisib, every day for 21 days. The first group of 3 will receive idelalisib 50 mg twice daily; the next cohort will receive idelalisib 100 mg twice daily; the last cohort will receive idelalisib 150 mg twice daily.
arm group label: Phase 2 Efficacy
arm group type: Experimental
description: All patients in the efficacy assessment phase will be treated with pembrolizumab (200 mg intravenously every 3 weeks) in combination with oral idelalisib (dose not exceeding 150 mg twice daily, per the phase 1 assessment) for 18 weeks before maintenance with pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, until disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Pembrolizumab
description: Anti PD-1 immunotherapeutic agent, which blocks a protective mechanism on cancer cells to allow the immune system to destroy cancer cells. Administered intravenously (IV).
arm group label: Phase 1 Dose Escalation
arm group label: Phase 2 Efficacy
other name: Keytruda
other name: MK-3475
intervention type: Drug
intervention name: Idelalisib
description: Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO).
arm group label: Phase 1 Dose Escalation
arm group label: Phase 2 Efficacy
other name: Zydelig
other name: GS-1101
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zhonglin Hao, MD, PhD
role: Principal Investigator
affiliation: Georgia Cancer Center
last name: Lisa Marshall, MSN, RN, CNL
phone: 706-721-5095
email: LMarshall@augusta.edu
last name: Carrie McAteer, BA, CCRC
phone: 706-721-1409
email: Cancer_Center_Trials@augusta.edu
facility: 
status: Recruiting
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Augusta University
investigator full name: Zhonglin Hao
investigator title: Associate Professor of Medicine, Cancer Biology; Leader, Thoracic Oncology Program, Georgia Cancer Center
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Neoplasm Metastasis
mesh term: Recurrence
mesh term: Pembrolizumab
mesh term: Idelalisib
sharing ipd: No
submitted: August 3, 2023
returned: August 25, 2023