Dose Evaluation of MK-1966 in Combination With SD-101 in Participants With Advanced Malignancies (MK-1966-001)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Neoplasms, Advanced

Treatments: Biological: MK-1966; Drug: SD-101

Study type: Interventional

Funder types: Industry

Identifiers

NCT02731742

MK-1966-001 (Other Identifier)

1966-001

Details and patient eligibility

About

This was a non-randomized, open-label study of MK-1966 used in combination with SD-101 in the treatment of advanced malignancies. The study included an initial Dose Evaluation phase (Part A) to determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) by evaluating Dose Limiting Toxicities (DLTs) of four dose combinations of MK-1966 and SD-101. Following determination of the MTD/MAD, approximately 20 participants each were to be enrolled in two expansion cohorts (Parts B or C) to confirm/refine the MTD/MAD. The study was terminated by the Sponsor before enrollment into Part A concluded and before enrollment into Parts B and C began.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a histologically- or cytologically-confirmed advanced malignancy that has progressed after standard-of-care therapy/treatments and there is no available therapy likely to convey clinical benefit
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Has a life expectancy ≥ 6 months
• Female participants must not be pregnant (negative urine or serum human chorionic gonadotropin test at screening and again within 72 hours prior to receiving the first dose of study therapy)
• Female and male participants of reproductive potential must agree to use adequate contraception during the course of the study through 120 days after study the last dose of study therapy
• Has ability to submit archived or fresh tumor sample during the screening period

Exclusion criteria

• Has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or who has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks earlier
• Has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of study start
• Is expected to require any other form of antineoplastic therapy while on study
• Is on chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication
• Has a history of a 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 had a severe hypersensitivity reaction to treatment with another monoclonal antibody
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has an active infection requiring therapy
• Has active, current pneumonitis, or a history of (non-infectious) pneumonitis that required steroids
• Has had a prior stem cell or bone marrow transplant
• Is positive for Human Immunodeficiency Virus (HIV) and/or Hepatitis B or C
• Has known psychiatric disorder that would interfere with fulfilling the requirements of the study
• Is a regular user of any illicit drugs or had a recent history of substance abuse
• Has symptomatic ascites or pleural effusion
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study
• Has clinically significant heart disease that affects normal activities
• Has had major surgery (requiring at least a 3 day hospital stay) in the past 28 days
• Has received a live vaccine within 30 days prior to first dose of study therapy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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14 participants in 6 patient groups

Dose A MK-1966 + Dose A SD-101

Experimental group

Description:

Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.

Treatment:

Biological: MK-1966

Drug: SD-101

Dose A MK-1966 + Dose B SD-101

Experimental group

Description:

Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.

Treatment:

Biological: MK-1966

Drug: SD-101

Dose B MK-1966 + Dose B SD-101

Experimental group

Description:

Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.

Treatment:

Biological: MK-1966

Drug: SD-101

Dose C MK-1966 + Dose B SD-101

Experimental group

Description:

Participants received a combination of MK-1966 (Days 1 and 21) and SD-101 (Days 1, 8, 15 and Day 22) in Part A of the study (approximately 21 days). Participants were to continue in one of two expansion cohorts (Part B or C) and receive up to 8 cycles of treatment (approximately 24 weeks). Each cycle was 21 days.

Treatment:

Biological: MK-1966

Drug: SD-101

Part B Expansion Cohort

Experimental group

Description:

Participants were to receive the MTD/MAD of MK-1966 and SD-101 established in Part A for up to 7 additional treatment cycles with MK-1966 and up to 6 additional treatment cycles with SD-101. Each cycle was to be 21 days.

Treatment:

Biological: MK-1966

Drug: SD-101

Part C Expansion Cohort

Experimental group

Description:

Participants were to receive the MTD/MAD of MK-1966 and SD-101 established in Part A for up to 7 additional treatment cycles with MK-1966 and 6 additional treatment cycles with SD-101. Each cycle was to be 21 days.

Treatment:

Biological: MK-1966

Drug: SD-101