Clinical Trials /

Crizotinib Plus Pembrolizumab In Alk-Positive Advanced Non Small Cell Lung Cancer Patients

NCT02511184

Description:

The purpose of this study has 2 phases, a Dose Finding Phase will determine the maximum tolerated dose . The Dose Expansion Phase will explore the safety, tolerability, and anti-tumor activity of the combination.

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

Terminated

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Crizotinib</span> Plus <span class="go-doc-concept go-doc-intervention">Pembrolizumab</span> In Alk-Positive Advanced Non Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> Patients

Title

  • Brief Title: Crizotinib Plus Pembrolizumab In Alk-Positive Advanced Non Small Cell Lung Cancer Patients
  • Official Title: A Phase 1b Study Of Crizotinib In Combination With Pembrolizumab (MK-3475) In Patients With Untreated Advanced Alk-Translocated Non Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02511184

    ORG ID: A8081054

    NCI ID: KEYNOTE 050

    Trial Conditions

    ALK-positive Advanced NSCLC

    Trial Interventions

    Drug Synonyms Arms
    Crizotinib Dose finding and dose expansion phases
    Pembrolizumab Dose finding and dose expansion phases

    Trial Purpose

    The purpose of this study has 2 phases, a Dose Finding Phase will determine the maximum
    tolerated dose . The Dose Expansion Phase will explore the safety, tolerability, and
    anti-tumor activity of the combination.

    Detailed Description

    The patients will be screened for up to 28 days before they start treatment to determine if
    they meet eligibility criteria. The screening procedures will include physical examination,
    blood work and radiological scans.

    In the dose finding phase, patients who meet eligibility criteria will receive crizotinib at
    the dose level assigned that will be taken on daily basis and pembrolizumab 200 mg
    intravenous infusion every 3 weeks.

    Once a Crizotinib dose level is decided, the dose expansion cohort will start enrolling
    patients who meet eligibility criteria.

    All patients will be followed up every three weeks. Blood samples will be drawn to test for
    safety and tumor activities and radiological scans will be performed on certain timepoints
    to determine the antitumor activities.

    There will be a quality of life questionnaire administered at certain time points during the
    study.

    The study will have a quality assurance plan that addresses data validation and registry
    procedures. There is a plan to visit the investigator site for routine monitoring and
    auditing.

    The team will conduct source data verification to assess the accuracy, completeness, or
    representativeness of registry data by comparing the data to external data sources (e.g.,
    medical records, paper or electronic case report forms, or interactive voice response
    systems).

    The study will also include a statistical analysis plan describing the analytical principles
    and statistical techniques to be employed in order to address the primary and secondary
    objectives of this study, as specified in the study protocol or statistical plan.

    Trial Arms

    Name Type Description Interventions
    Dose finding and dose expansion phases Experimental Find and expand the maximum tolerated dose of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks. Crizotinib, Pembrolizumab

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically proved diagnosis of locally advanced recurrent or
    metastatic non-squamous NSCLC that is not suitable for local curative treatment.

    - Alk-positive NSCLC as determined by a test that is approved or validated for use as a
    companion diagnostic test.

    - No prior systemic therapy for metastatic disease.

    - Adjuvant chemotherapy more than 12 months prior to study enrollment.

    - Measurable disease as per RECIST 1.1

    - ECOG PS 0 or 1.

    Exclusion Criteria:

    - Prior exposure to ALK receptor tyrosine kinase inhibitor, anti-PD1, anti-PDL1 or any
    drug targeting T-cell checkpoint pathways.

    - known diagnosis of immunodeficiency or is receiving systemic steroid therapy or other
    form of immunosuppressive therapy within 7 days of clinical trial treatment.

    - Active autoimmune disease that has required systemic treatment in the past 3 months.

    - History of extensive disseminated interstitial fibrosis or any grade of interstitial
    lung disease.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 99 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Dose Limiting Toxicities (DLT)

    Secondary Outcome Measures

    Objective Response Rate (ORR)

    Duration of Response (DR)

    Time to Tumor Response (TTR)

    Progression-Free Survival (PFS)

    PDL1 Expression

    Pembrolizumab Ctrough

    Crizotinib (Ctrough)

    Crizotinib Cmax

    Crizotinib Tmax

    Crizotinib AUC(0-8)

    Crizotinib AUC Tau

    Crizotinib CL/F

    PF--06260182 Cmax

    PF--06260182 Tmax

    PF--06260182 Ctrough

    PF--06260182 AUC

    PF--06260182 MRCmax

    PF--06260182 MRAUCtau

    PF--06260182 AUCtau

    Trial Keywords

    crizotinib

    pembrolizumab

    ALK-positive NSCLC

    Lung Cancer

    ALK-translocated NSCLC

    Non Small Cell Lung Cancer