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Pembrolizumab + Idelalisib for Lung Cancer Study (PIL)

Primary Purpose

Non Small Cell Lung Cancer, Metastasis, Recurrence

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Idelalisib
Sponsored by
Zhonglin Hao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Non Small Cell Lung Cancer, Metastasis, Recurrence, Immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

All subjects must have documented metastatic or recurrent NSCLC from biopsy. They must have failed or progressed on platinum-based chemotherapy (e.g. cisplatin, carboplatin) as well as immune checkpoint inhibitor therapy (e.g nivolumab or pembrolizumab). Patients with EGFR/ALK mutations/translocations must have failed or progressed on small molecule inhibitor therapies (e.g. erlotinib, afatinib, etc.).

Inclusion Criteria:

  • Have at least one measurable lesion
  • Have an ECOG Performance Status of 1 or less
  • Demonstrate adequate organ function as defined in the protocol.
  • Female subjects of childbearing potential must have a negative pregnancy test before starting treatment; they must also be willing to use two methods of birth control or abstain from heterosexual activity for the duration of the study.
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through the duration of the study.

Exclusion Criteria:

  • Is currently receiving study drug in another trial; or has participated in an investigational drug study within 3 weeks of the first dose of treatment.
  • Is within 3 weeks of most recent chemotherapy.
  • Has a history of hypersensitivity to pembrolizumab or idelalisib, or any of their excipients.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated, stable, brain metastases may participate; carcinomatous meningitis is excluded regardless of clinical stability.
  • Has known history of non-infectious pneumonitis that required steroid use or has current pneumonitis.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Has active autoimmune disease that has required treatment; known history of Human Immunodeficiency Virus (HIV); known active Hepatitis B or Hepatitis C.
  • Has an active infection requiring systemic therapy.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial

Sites / Locations

  • Georgia Cancer Center at Augusta UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1 Dose Escalation

Phase 2 Efficacy

Arm 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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03
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.

Secondary Outcome Measures

Dose-Finding Assessment for optimum dose of idelalisib in combination with pembrolizumab
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.
Overall Response Rates (ORR) to combination therapy
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.

Full Information

First Posted
August 16, 2017
Last Updated
September 27, 2017
Sponsor
Zhonglin Hao
Collaborators
Merck Sharp & Dohme LLC, Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03257722
Brief Title
Pembrolizumab + Idelalisib for Lung Cancer Study
Acronym
PIL
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Recruiting
Study Start Date
September 26, 2017 (Actual)
Primary Completion Date
August 2020 (Anticipated)
Study Completion Date
August 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zhonglin Hao
Collaborators
Merck Sharp & Dohme LLC, Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Metastasis, Recurrence
Keywords
Non Small Cell Lung Cancer, Metastasis, Recurrence, Immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Dose Escalation
Arm Type
Experimental
Arm 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 Title
Phase 2 Efficacy
Arm Type
Experimental
Arm 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(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, MK-3475
Intervention 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).
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
Zydelig, GS-1101
Intervention Description
Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO).
Primary Outcome Measure Information:
Title
Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03
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.
Time Frame
First 9 weeks at each dose level
Secondary Outcome Measure Information:
Title
Dose-Finding Assessment for optimum dose of idelalisib in combination with pembrolizumab
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.
Time Frame
18-27 weeks
Title
Overall Response Rates (ORR) to combination therapy
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.
Time Frame
18 weeks - 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
All subjects must have documented metastatic or recurrent NSCLC from biopsy. They must have failed or progressed on platinum-based chemotherapy (e.g. cisplatin, carboplatin) as well as immune checkpoint inhibitor therapy (e.g nivolumab or pembrolizumab). Patients with EGFR/ALK mutations/translocations must have failed or progressed on small molecule inhibitor therapies (e.g. erlotinib, afatinib, etc.). Inclusion Criteria: Have at least one measurable lesion Have an ECOG Performance Status of 1 or less Demonstrate adequate organ function as defined in the protocol. Female subjects of childbearing potential must have a negative pregnancy test before starting treatment; they must also be willing to use two methods of birth control or abstain from heterosexual activity for the duration of the study. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through the duration of the study. Exclusion Criteria: Is currently receiving study drug in another trial; or has participated in an investigational drug study within 3 weeks of the first dose of treatment. Is within 3 weeks of most recent chemotherapy. Has a history of hypersensitivity to pembrolizumab or idelalisib, or any of their excipients. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated, stable, brain metastases may participate; carcinomatous meningitis is excluded regardless of clinical stability. Has known history of non-infectious pneumonitis that required steroid use or has current pneumonitis. Has a known history of active TB (Bacillus Tuberculosis) Has active autoimmune disease that has required treatment; known history of Human Immunodeficiency Virus (HIV); known active Hepatitis B or Hepatitis C. Has an active infection requiring systemic therapy. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Marshall, MSN, RN, CNL
Phone
706-721-5095
Email
LMarshall@augusta.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Carrie McAteer, BA, CCRC
Phone
706-721-1409
Email
Cancer_Center_Trials@augusta.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhonglin Hao, MD, PhD
Organizational Affiliation
Georgia Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgia Cancer Center at Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Pembrolizumab + Idelalisib for Lung Cancer Study

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