Clinical Trials /

Phase II Trial of Continuation Therapy in Advanced NSCLC

NCT03083808

Description:

This is a single-arm phase II study of continuation immunotherapy with pembrolizumab following initial benefit (CR, PR, or SD ≥ 3 months) with a PD-1 or PD-L1 inhibitor.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Trial of Continuation Therapy in Advanced NSCLC
  • Official Title: A Phase II Trial of Chemotherapy Plus Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Previously Treated With PD-1 or PD-L1 Inhibitor: Big Ten Cancer Research Consortium BTCRC-LUN15-029

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-LUN15-029
  • NCT ID: NCT03083808

Conditions

  • Non-Small-Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytruda®, MK-3475Pembrolizumab 200mg IV every 21 days

Purpose

This is a single-arm phase II study of continuation immunotherapy with pembrolizumab following initial benefit (CR, PR, or SD ≥ 3 months) with a PD-1 or PD-L1 inhibitor.

Detailed Description

      OUTLINE: This is a multi-center study.

      Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3
      months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of
      each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every
      three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine
      1000mg/m2 IV D1 and D8 every three weeks, docetaxel 75mg/m2 IV D1 every three weeks, or
      pemetrexed 500mg/m2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only).
      Subjects will continue to receive this combination until progression or intolerable toxicity.

      Administration Sequence: First Sequence

      - Pembrolizumab 200mg IV on Day 1 (cycle = 21 days)

      Administration Sequence: Second Sequence

        -  Gemcitabine 1000mg/m^2 IV on Days 1,8 (cycle = 21 days)

        -  Docetaxel 75mg/^2 IV on Days 1,8 (cycle = 21 days)

        -  Pemetrexed 500mg/m^2 IV on Day 1 (cycle -= 21 days)
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab 200mg IV every 21 daysExperimentalPatients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m^2 IV D1 and D8 every three weeks, docetaxel 75mg/m^2 IV D1 every three weeks, or pemetrexed 500mg/m^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        Subjects must meet all of the following applicable inclusion criteria to participate in
        this study:

          -  Written informed consent and HIPAA authorization for release of protected health
             information.

          -  Age ≥ 18 years at the time of consent.

          -  Histological or cytological evidence of stage IV NSCLC (any histology)

          -  Subjects must have progressed on or after previous platinum-based chemotherapy.
             Chemotherapy may have previously been given with a PD-1 or PD-L1 inhibitor. Subjects
             must have also progressed on or after receiving any PD-1 or PD-L1 inhibitor (including
             pembrolizumab) as their most recent therapy and must have had at least a 3-month PFS
             on this therapy.

          -  Subjects must be enrolled on the trial within 6 weeks of their last infusion of PD-1
             or PD-L1 inhibitor therapy.

          -  Subjects whose tumors harbor a mutation in EGFR exon 19 or 21 or have gene
             rearrangements in ALK or ROS1 must have already been treated with standard targeted
             therapies. NOTE: Subjects must also have progressed on or after platinum-containing
             combination chemotherapy.

          -  ECOG Performance Status of 0 or 1 within 28 days prior to registration for protocol
             therapy.

          -  Must be fit enough to receive next-line chemotherapy (either gemcitabine, docetaxel,
             or pemetrexed [non-squamous only]) according to the discretion of the treating
             physician.

          -  Adequate laboratory values obtained within 28 days prior to registration for protocol
             therapy.

          -  Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy
             test within 7 days prior to study registration and/or within 72 hours of first dose of
             study drugs. If the urine test is positive or cannot be confirmed as negative, a serum
             pregnancy test will be required.

          -  Women of childbearing potential must be willing to use two methods of contraception or
             abstain from heterosexual activity from the point of registration through 120 days
             after the last dose of study drug.

          -  Male subjects capable of fathering a child must agree to use an adequate method of
             contraception starting with the first dose of the study drug through 120 days after
             the last dose of the study drug.

        Exclusion Criteria:

        Subjects meeting any of the criteria below may not participate in the study:

          -  Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Active central nervous system (CNS) metastases. NOTE: Subjects who are symptomatic or
             have not undergone prior brain imaging must undergo a head computed tomography (CT)
             scan or brain MRI within 28 days prior to registration to exclude brain metastases.

          -  Treatment with any investigational agent within 28 days prior to registration for
             protocol therapy with the exception of PD-1 or PD-L1 inhibitors.

          -  No active second cancers with the exception of localized non-melanoma skin cancer,
             in-situ cervical or in-situ bladder cancer.

          -  Evidence of active autoimmune disease requiring systemic treatment within the past 90
             days or a documented history of clinically severe autoimmune disease, or a syndrome
             that requires systemic steroids or immunosuppressive agents.

          -  History of (non-infectious) pneumonitis requiring treatment with corticosteroids,
             evidence of interstitial lung disease or active, non-infectious pneumonitis.

          -  History of an immune-related toxicity requiring treatment with corticosteroids during
             prior PD-1/ PD-L1 inhibitor treatment.

          -  Diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy
             or other immunosuppressive therapy (excludes inhaled corticosteroids) within 7 days of
             study registration.

          -  History of psychiatric illness or social situations that would limit compliance with
             study requirements.

          -  Clinically active infection (≥ Grade 2) as judged by the site investigator.

          -  Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B
             or C. NOTE: HIV, HBV or HCV testing is not required.

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the trial, interfere with the subject's participation
             for the full duration of the trial, or is not in the best interest of the subject to
             participate, in the opinion of the site investigator.

          -  Known history of active TB (Bacillus Tuberculosis).

          -  History of hypersensitivity to pembrolizumab, docetaxel, gemcitabine, pemetrexed or
             any of their excipients.

          -  Has received a live vaccine within 30 days prior to planned start of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:3 months
Safety Issue:
Description:A measurement from the date of treatment start until the criteria for disease progression is met as defined by RECIST 1.1 or death occurs

Secondary Outcome Measures

Measure:Clinical Benefit Rate (CBR)
Time Frame:3 months
Safety Issue:
Description:any subject with stable disease for ≥ 3 months, partial response, or complete response assessed via RECISIT 1.1 and irRECIST
Measure:Objective Response Rate (ORR)
Time Frame:1 year
Safety Issue:
Description:The ORR is the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence
Measure:Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:Overall survival is defined by the date of treatment start to date of death from any cause
Measure:Assess Toxicity
Time Frame:2 years
Safety Issue:
Description:Toxicity will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Greg Durm, MD

Trial Keywords

  • PD-1
  • PD-L1 Inhibitor
  • Pembrolizumab
  • Docetaxel
  • Pemetrexed
  • Gemcitabine

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