Clinical Trials /

Pembrolizumab + Idelalisib for Lung Cancer Study

NCT03257722

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. 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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab + Idelalisib for Lung Cancer Study
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GCC-16053
  • NCT ID: NCT03257722

Conditions

  • Non Small Cell Lung Cancer
  • Metastasis
  • Recurrence

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475Phase 1 Dose Escalation
IdelalisibZydelig, GS-1101Phase 1 Dose Escalation

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose EscalationExperimentalSequential 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.
  • Pembrolizumab
  • Idelalisib
Phase 2 EfficacyExperimentalAll 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.
  • Pembrolizumab
  • Idelalisib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
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.

Secondary Outcome Measures

Measure:Dose-Finding Assessment for optimum dose of idelalisib in combination with pembrolizumab
Time Frame:18-27 weeks
Safety Issue:
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
Safety Issue:
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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Zhonglin Hao

Trial Keywords

  • Non Small Cell Lung Cancer
  • Metastasis
  • Recurrence
  • Immunotherapy

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