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Study of MK-4280 as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy AND MK-4280A as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001)

Trial Status: Active

This is a safety and pharmacokinetics study of MK-4280 as monotherapy and in combination with pembrolizumab (MK-3475) AND MK-4280A as monotherapy in adults with metastatic solid tumors for which there is no available therapy which may convey clinical benefit. Part A of this study is a dose escalation design in which participants receive MK-4280 as monotherapy or MK-4280 in combination with pembrolizumab. Part B is a dose confirmation design to estimate the recommended Phase 2 dose (RPTD), as determined by dose-limiting toxicity, for MK-4280 in combination with pembrolizumab in participants with advanced solid tumors. Part B will also assess the efficacy of MK-4280 as monotherapy and in combination with pembrolizumab with and without chemotherapy AND MK-4280A as monotherapy in expansion cohorts.

Inclusion Criteria

  • Part A and Part B: Has histologically or cytologically-confirmed metastatic solid tumor.
  • Has measurable disease by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria.
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrates adequate organ function
  • If female of child-bearing potential, is willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
  • If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Exclusion Criteria

  • Has had chemotherapy, radiation or biological cancer therapy within 4 weeks prior to the first dose of study drug, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 0 or 1 from the AEs due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related [ir]AEs).
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
  • Has received previous treatment with another agent targeting the lymphocyte-activation gene 3 (LAG-3) receptor.
  • Has received previous treatment with an immunomodulatory therapy (e.g. anti-programmed cell death-1/anti-programmed cell death-ligand 1 [anti-PD-1/anti-PD-L1] or cytotoxic T-lymphocyte-associated protein 4 [CTLA 4] agent) and was discontinued from that therapy due to a Grade 3 or higher irAE.
  • Is expected to require any other form of antineoplastic therapy while on study.
  • Has a diagnosis of immunodeficiency or is receiving 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. Time frame exceptions include successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in situ cancers.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • Has an active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
  • Has an active infection requiring therapy.
  • Has history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has had a prior stem cell or bone marrow transplant.
  • Has a known history of or screens positive for Human Immunodeficiency Virus (HIV), active chronic or acute Hepatitis B or Hepatitis C.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • Is a regular user as determined by investigator judgment (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent.
  • Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.
  • Has clinically significant heart disease that affects normal activities.
  • Has had major surgery in the past 4 weeks.
  • Has received a live-virus vaccine within 30 days of planned start of study drug. Seasonal flu vaccines that do not contain live virus are permitted.

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Florida

Jacksonville
Mayo Clinic in Florida
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Merck and Company Inc

  • Primary ID 4280-001
  • Secondary IDs NCI-2017-02413, 183971, MK-4280-001, 2017-001464-38
  • Clinicaltrials.gov ID NCT02720068