Study of MK-7684 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001)

Status: Active

Description

This is a safety, efficacy, and pharmacokinetics study of MK-7684 as monotherapy and in combination with pembrolizumab (MK-3475) or pembrolizumab plus pemetrexed and carboplatin in adults with metastatic solid tumors for which there is no available therapy that is expected to convey clinical benefit. Part A of this study is a dose escalation and confirmation phase to estimate the recommended Phase 2 dose (RPTD) for MK-7684 monotherapy or in combination with pembrolizumab, pemetrexed, and carboplatin. Part A will also evaluate the anti-tumor activity of MK-7684 in combination with pembrolizumab plus pemetrexed and carboplatin in participants with non-small cell lung cancer (NSCLC) and MK-7684 (at two dose levels) in combination with pembrolizumab in Japanese participants with gastric cancer. Part B will evaluate the anti-tumor activity of MK-7684 at the RPTD when used as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors in a non-randomized study design. Part B will also evaluate 2 doses of MK-7684 in combination with pembrolizumab in participants with programmed death 1 (PD-1) treatment naïve cancer using a 1:1 randomized study design. The primary hypothesis is that MK-7684 administered as monotherapy or in combination with pembrolizumab is safe when administered at the RPTD.

Eligibility Criteria

Inclusion Criteria

  • For Part A Japanese cohort added with Amendment 7: Must reside in Japan and be of Japanese descent and have adenocarcinoma of the stomach and/or gastric-esophageal junction (GEJ) that is considered inoperable and that has received, and progressed on, at least 1 prior chemotherapy regimen or human epidermal growth factor receptor 2 (HER2)/neu-targeted approved therapy (if HER2/neu-positive). In both cases, participants may be untreated or could have received and progressed on 1 prior regimen, but must not have received prior anti-PD-1/PD-L1 therapy
  • For Part A participants with NSCLC added with Amendment 7: Must have a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per current AJCC criteria, edition 8) non-squamous NSCLC
  • For Parts A and B: Has histologically or cytologically confirmed metastatic solid tumor
  • Has measureable disease by Response Evaluation Criteria In Solid Tumors (RECIST)
  • Has an Eastern Cooperative Oncology Group performance status of 0 to 1
  • Females must not be pregnant
  • Women of childbearing potential and male participants must agree to use adequate contraception for the course of the study
  • Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)

Exclusion Criteria

  • Has had chemotherapy, radiation, biological cancer therapy or major surgery within 4 weeks prior to the first dose of study treatment
  • Has not recovered to Common Toxicity Criteria for Adverse Events Grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks prior to the first dose of study treatment
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
  • Has received previous treatment with another agent targeting the T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (TIGIT) receptor
  • Has received previous treatment with an immunomodulatory agent (e.g., anti-programmed cell death 1/ anti-programmed cell death ligand 1 or cytotoxic T-lymphocyte-associated protein 4) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event
  • Is expected to require any other form of antineoplastic therapy while participating in the trial
  • Is on chronic systemic steroid therapy in excess of replacement doses or on any other form of immunosuppressive medication.
  • Has a history of a previous additional malignancy unless potentially curative treatment has been completed with no evidence of malignancy for 5 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease
  • Has an active infection requiring systemic treatment
  • Has interstitial lung disease
  • Has active or past history of (non-infectious) pneumonitis requiring steroids
  • Has symptomatic ascites or pleural effusion
  • Has previously had a hematopoetic stem cell transplant or solid organ transplant
  • Is known to be human immunodeficiency virus (HIV) positive and/or known to have active chronic or acute Hepatitis B or Hepatitis C
  • Has a known psychiatric and/or substance abuse disorder that would make it difficult for the participant to cooperate with the requirements of the trial
  • Is a regular user (including recreational use) of any illicit drugs at the time of signing informed consent, or has a recent history (within the last year) of substance abuse
  • Has received a live-virus vaccine within 30 days prior to the first dose of study treatment
  • Has had hormonal cancer therapy (e.g., tamoxifen, leuprolide). within 4 weeks prior to the first dose of study treatment
  • For Part A participants with NSCLC added with Amendment 7: Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) other than an aspirin dose ≤1.3 gram per day for a 5-day period (8-day period for long-acting agents, such as piroxicam)
  • For Part A participants with NSCLC added with Amendment 7: Is unable or unwilling to take folic acid or Vitamin B12 supplementation

Locations & Contacts

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Name Not Available

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

Connecticut

New Haven
Yale University
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Merck and Company Inc

Trial IDs

Primary ID 7684-001
Secondary IDs NCI-2017-01823, MK-7684-001, 194809
Clinicaltrials.gov ID NCT02964013