Clinical Trials /

Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)

NCT02349633

Description:

This is a Phase 1/2 study of PF-06747775 as a single agent and in combination with other cancer treatments in patients with advanced EGFRm NSCLC. The overall clinical study consists of a Phase 1 single agent dose-escalation and expansion part to determine the RP2D of PF-06747775 single agent in patients with previously-treated EGFRm NSCLC followed by sequential evaluations of PF-06747775 at the RP2D in 3 different clinical scenarios as detailed below: - Cohort 1: Phase 2 evaluation of PF-06747775 as a single agent in previously untreated patients with advanced EGFRm NSCLC, - Cohort 2: Phase 1b single arm evaluation of PF-06747775 in combination with palbociclib (Cohort 2A) followed by Phase 2 randomized evaluation of PF 06747775 in combination with palbociclib vs PF-06747775 single agent (Cohort 2B) in previously-treated patients with EGFRm NSCLC with a secondary T790M mutation (del 19 and T790M or L858R and T790M), and - Cohort 3: Phase 1b evaluation of PF-06747775 in combination with avelumab in previously-treated patients with EGFRm NSCLC with a secondary T790M mutation (del 19 and T790M or L858R and T790M).

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study For Patients With NSCLC <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-keyword">Mutations</span> (Del 19 or L858R +/- T790M)

Title

  • Brief Title: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)
  • Official Title: Phase 1/2 Open-Label Study Of PF-06747775 (Epidermal Growth Factor Receptor T790M Inhibitor) In Patients With Advanced Epidermal Growth Factor Receptor (EGFR) Mutant (Del 19 Or L858R +/- T790M) Advanced Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02349633

    ORG ID: B7971001

    Trial Conditions

    Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    PF-06747775 Single Arm - study drug

    Trial Purpose

    Phase 1: The Phase 1 study is an open label, multi center, multiple dose, non randomized,
    safety, pharmacokinetic, and pharmacodynamics dose escalation study of PF 06747775 as a
    single agent in patients with advanced EGFRm NSCLC (del19 or L858R, +/ -T790M).

    Phase 2: an open label, multi-center, single arm study of PF-06747775 for the assessment of
    anti-tumor activity in patients with advanced EGFRm (del19 or L858R) advanced NSCLC with
    T790M (del 19 and T790M or L858R and T790M) and further pharmacokinetic characterization.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Single Arm - study drug Experimental The study will evaluate single agent PF-06747775 PF-06747775

    Eligibility Criteria

    Inclusion criteria (partial list):

    - Evidence of histologically or cytologically confirmed diagnosis of locally advanced
    or metastatic EGFRm (del19 or L858R) NSCLC that has progressed after at least 1 prior
    line of therapy.

    - Patients must have had disease progression on treatment with an approved EGFR TKI.

    - In Phase 1, patients may have also received other lines of therapy before or
    after the EGFR TKI.

    - In Phase 2, while patients may have had multiple lines of therapy, the last
    therapy prior to study treatment must have been an approved EGFR TKI and
    received within 6 weeks prior to study registration.

    - In the Phase 1 portion:

    - In the dose escalation and MTD expansion portions patients must be T790M
    positive or unknown status.

    - In the PK sub-studies, patients with EGFRm (del 19 or L858R) with any T790M
    status are eligible to enroll.

    - In the Phase 2 portion:

    Patients must have EGFRm (del 19 and T790M or L858R and T790M) NSCLC tumors

    - Patients must have at least one measurable lesion as defined by RECIST version 1.1

    - Tumor tissue available (ie, formalin fixed paraffin embedded (FFPE) block or 10
    unstained sections (5 micron). An archival specimen is acceptable for Phase 1; a de
    novo specimen is required for Phase 2.

    - Patients must have adequate bone marrow, hepatic and renal functions

    - Negative serum pregnancy test

    Exclusion Criteria (partial list)

    - Previously diagnosed brain metastases, unless the patient has completed their
    treatment and has recovered from the acute effects of radiation therapy or surgery
    prior to study registration, have discontinued corticosteroid treatment for these
    metastases for at least 2 weeks, and are neurologically stable.

    - Major surgery within 4 weeks prior to registration

    - Radiation therapy within 2 weeks prior to registration.

    - Systemic anti cancer therapy within 2 weeks or 5 half-lives (whichever is longer) of
    registration excluding EGFR TKIs. Patients on EGFR TKIs must discontinue the agent
    for a minimum of 5 half-lives, or 5 days, whichever is longer, prior to registration

    - Concurrent use of drugs that are strong P-glycoprotein (P-gp) inhibitors (such as but
    not limited to: dronedarone, erythromycin, indinavir, indinavir/ritonavir,
    itraconazole, ketoconazole, lapatinib, lopinavir/ritonavir, quinidine, rifampin,
    ritonavir, valspodar, verapamil, vorapaxar). Patients must avoid the use of drugs
    that are known strong P-gp inhibitors for the duration of the study. therapy with a
    T790M directed agent

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phase 1 Primary Endpoint - Number of patients with dose limiting toxicities during Phase 1

    Phase 2: Number of patients with Objective Response

    Secondary Outcome Measures

    Phase 1: Secondary Endpoint - Number of patients with Objective Response (OR)

    Phase 2: Progression Free Survival (PFS)

    Trial Keywords

    EGFRm - Epidermal Growth Factor Receptor Mutation

    Advanced EGFRm (del19 or L858R +/- T790M NSCLC