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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/1b Trial of MK-1966 in Combination With SD-101 in Subjects With Advanced Malignancies

Conditions
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Neoplasms, Advanced

Intervention / Treatment
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* Biological: MK-1966
* Drug: SD-101


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose A MK-1966 + Dose A SD-101<br>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. | Biological: MK-1966<br>* MK-1966 administered as an intravenous (IV) infusion<br>Drug: SD-101<br>* SD-101 administered as an intratumoral (IT) injection<br>|
| Experimental: Dose A MK-1966 + Dose B SD-101<br>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. | Biological: MK-1966<br>* MK-1966 administered as an intravenous (IV) infusion<br>Drug: SD-101<br>* SD-101 administered as an intratumoral (IT) injection<br>|
| Experimental: Dose B MK-1966 + Dose B SD-101<br>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. | Biological: MK-1966<br>* MK-1966 administered as an intravenous (IV) infusion<br>Drug: SD-101<br>* SD-101 administered as an intratumoral (IT) injection<br>|
| Experimental: Dose C MK-1966 + Dose B SD-101<br>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. | Biological: MK-1966<br>* MK-1966 administered as an intravenous (IV) infusion<br>Drug: SD-101<br>* SD-101 administered as an intratumoral (IT) injection<br>|
| Experimental: Part B Expansion Cohort<br>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. | Biological: MK-1966<br>* MK-1966 administered as an intravenous (IV) infusion<br>Drug: SD-101<br>* SD-101 administered as an intratumoral (IT) injection<br>|
| Experimental: Part C Expansion Cohort<br>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. | Biological: MK-1966<br>* MK-1966 administered as an intravenous (IV) infusion<br>Drug: SD-101<br>* SD-101 administered as an intratumoral (IT) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Dose Limiting Toxicity (DLT) | The occurrence of any of the following toxicities during Cycle 1 (Days 1-21), if assessed by the Investigator to be possibly, probably or definitely related to MK-1966 or SD-101, was considered a DLT: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting >7 days, except thrombocytopenia: *Gr 4 thrombocytopenia of any duration; *Gr 3 thrombocytopenia if associated with bleeding; Gr 3 non-hematologic toxicity lasting >3 days despite optimal supportive care; Any Gr 3 or Gr 4 non-hematologic laboratory abnormality, if: medical intervention is required OR abnormality leads to hospitalization OR abnormality persists for >1 week; Febrile neutropenia Gr 3 or Gr 4; Any drug-related AE which caused participant to discontinue study drug during Cycle 1 Gr 5 toxicity; or Delay in initiation of Cycle 2 for >2 weeks due to study drug-related toxicity. The percentage of participants who experienced a DLT during Cycle 1 is presented. | From time of first dose of study drug to the end of Cycle 1. Each cycle was 21 days. (Up to 21 days) | 
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study drug or protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study drug, was also an AE. The number of participants who experienced as AE is presented. | From first dose of study drug through 90 days after last dose of study drug (Up to approximately 22 weeks) | 
| Number of Participants Discontinuing Study Drug Due to AEs | The number of participants who discontinued study drug due to an AE is presented. | From first dose of study drug up to last dose of study drug (Up to approximately 9 weeks) |