Clinical Trials /

A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) in Subjects With Selected Cancers (INCB 24360-202 / MK-3475-037 / KEYNOTE-037/ ECHO-202)

NCT02178722

Description:

The purpose of this study is to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in subjects with certain cancers. This study will be conducted in 2 phases, Phase 1 and Phase 2.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of <span class="go-doc-concept go-doc-intervention">MK-3475</span> in Combination With INCB024360 in Subjects With Selected Solid Tumors and Advanced NSCLC (INCB 24360-202 / <span class="go-doc-concept go-doc-intervention">MK-3475</span>-037 / KEYNOTE-037)

Title

  • Brief Title: A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of MK-3475 in Combination With INCB024360 in Subjects With Selected Solid Tumors and Advanced NSCLC (INCB 24360-202 / MK-3475-037 / KEYNOTE-037)
  • Official Title: A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of MK-3475 in Combination With INCB024360 in Subjects With Selected Solid Tumors (Phase 1) Followed by a Randomized, Double-Blind, Placebo-Controlled Study in Subjects With Advanced NSCLC (Phase 2)
  • Clinical Trial IDs

    NCT ID: NCT02178722

    ORG ID: INCB 24360-202

    Trial Conditions

    Cancer, Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    INCB024360 Phase 1: MK-3475 2 mg/kg + INCB024360 25 mg BID, Phase 2: MK-3475 selected dose + INCB024360
    MK-3475 Phase 1: MK-3475 2 mg/kg + INCB024360 25 mg BID, Phase 2: MK-3475 selected dose + Placebo, Phase 2: MK-3475 selected dose + INCB024360
    Placebo Phase 2: MK-3475 selected dose + Placebo

    Trial Purpose

    This study will be conducted in 2 phases. Phase 1 will include subjects with several
    different advanced or metastatic solid tumors and will test different doses of INCB024360 in
    combination with MK-3475 in order to select a dose for further evaluation. Phase 2 will
    include patients with advanced NSCLC only and will be randomized, double-blind and
    placebo-controlled utilizing the dose selected in Phase 1 to further evaluate the efficacy
    of this combination of MK-3475 and INCB024360.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Phase 1: MK-3475 2 mg/kg + INCB024360 25 mg BID Experimental Experimental: MK-3475 2 mg/kg given once every 3 weeks + INCB024360 25 mg BID as starting dose, followed by dose escalations (Phase 1) until recommended phase 2 dose of INCB024360 is determined INCB024360, MK-3475
    Phase 2: MK-3475 selected dose + Placebo Experimental Experimental: MK-3475 selected dose given once every 3 weeks + Placebo MK-3475, Placebo
    Phase 2: MK-3475 selected dose + INCB024360 Experimental MK-3475 selected dose given once every 3 weeks + INCB024360 (recommended phase 2 dose) INCB024360, MK-3475

    Eligibility Criteria

    Inclusion Criteria:

    - Subjects with histologically or cytologically NSCLC, melanoma, transitional cell
    carcinoma of the GU tract, renal cell cancer, triple negative breast cancer,
    adenocarcinoma of the endometrium or squamous cell carcinoma of the head and neck
    (Phase 1)

    - Subjects with histologically or cytologically Stage IIIb, IV, or recurrent NSCLC
    (Phase 2)

    - Life expectancy > 12 weeks.

    - Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.

    - Presence of measurable disease per Response Evaluation Criteria in Solid Tumors
    (RECIST) 1.1

    - Laboratory and medical history parameters within protocol-defined range.

    - For Phase 1: Subjects who have advanced or metastatic disease as noted above that
    have received at least one prior therapy or have advanced or metastatic disease for
    which no curative treatment is available may be enrolled.

    - For Phase 2: Subjects who have received only 1 prior systemic chemotherapy regimen
    for Stage IIIb, IV, or recurrent NSCLC (not including neo-adjuvant and/or adjuvant
    therapy). Prior systemic therapies must include a platinum-based regimen. Tumors with
    driver mutations (EGFR mutation positive or anaplastic lymphoma kinase fusion
    oncogene positive) treated with a tyrosine kinase inhibitor are permitted and will
    not be considered a second systemic chemotherapy regimen.

    - Tumor biopsies are required

    - Females of child-bearing potential and males who use adequate birth control through
    120 days post dose.

    Exclusion Criteria:

    - Subjects who participated in any other study in which receipt of an investigational
    study drug or device occurred within 28 days or 5 half-lives (whichever is longer)
    prior to first dose.

    - Subjects who have received more than one prior systemic treatment for Stage IIIb, IV,
    or recurrent NSCLC (Phase 2).

    - Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
    anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
    ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
    or checkpoint pathways).

    - Has known active central nervous system (CNS) metastases and/or carcinomatous
    meningitis. Subjects with previously treated brain metastases may participate
    provided they are stable

    - Has an active autoimmune disease.

    - Has evidence of interstitial lung disease or pneumonitis.

    - Live vaccine use within 30 days of first dose of study medication

    - Monoamine oxidase inhibitors

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phase 1: Number of subjects with dose limiting toxicities (DLTs) of INCB024360 in combination with MK-3475

    Phase 2: Progression free survival (PFS)

    Secondary Outcome Measures

    Objective response rate

    Number of subjects with Adverse Events as a Measure of Safety and Tolerability of INCB024360 in combination with MK-3475

    Overall survival (OS)

    Trial Keywords