Study of MK-1248 With and Without Pembrolizumab (MK-3475) for Participants With Advanced Solid Tumors (MK-1248-001)

NCT ID: NCT02553499

Last Updated: 2019-11-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-12
• Study Completion Date: 2018-10-17

Brief Summary

In this study, participants with advanced solid tumors were assigned to receive escalating doses of either MK-1248 alone or MK-1248 in combination with pembrolizumab (MK-3475). This study used the number of dose-limiting toxicities (DLTs) at each dose level to find and confirm the maximum tolerated dose (or maximum administered dose) for MK-1248 alone and in combination with pembrolizumab.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MK-1248

Participants received escalating doses of MK-1248 at assigned dose (dose range: 0.12 mg to 170 mg MK-1248) via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to \~3 months).

Group Type: EXPERIMENTAL

MK-1248

Intervention Type: BIOLOGICAL

IV infusion

MK-1248 + Pembrolizumab

Participants received escalating doses of MK-1248 at assigned dose (dose range: 0.12 mg to 60 mg MK-1248) via IV infusion on Day 1 of each 21-day cycle for a maximum of 4 cycles (up to \~3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~24 months).

Group Type: EXPERIMENTAL

MK-1248

Intervention Type: BIOLOGICAL

IV infusion

pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Interventions

MK-1248

IV infusion

Intervention Type: BIOLOGICAL

pembrolizumab

IV infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

KEYTRUDA®; MK-3475

Eligibility Criteria

Inclusion Criteria

• Histologically- or cytologically-confirmed metastatic solid tumor for which there is no available therapy that may convey clinical benefit
• Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Adequate organ function
• Female participants of childbearing potential should be willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication
• Male participants should agree to use adequate contraception starting with the first dose of study therapy through 180 days after the last dose of study medication
• Can submit a baseline tumor sample

Exclusion Criteria

• Has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study medication, or not recovered from adverse events due to cancer therapeutics administered more than 4 weeks earlier
• 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 medication
• Previous treatment with another agent targeting the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) receptor
• Previous treatment with an immunomodulatory therapy and was discontinued from that therapy due to an immune-related adverse event
• Expected to require any other form of antineoplastic therapy while on study
• On chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication
• History of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years with the exception of successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Severe hypersensitivity reaction to treatment with another monoclonal antibody
• Active autoimmune disease or a documented history of autoimmune disease with the exception of vitiligo or resolved childhood asthma/atopy, or endocrine deficiency following treatment with an immunomodulatory agent
• Active infection requiring therapy
• Active or a history of non-infectious pneumonitis
• Prior stem cell or bone marrow transplant
• Known history of human immunodeficiency virus (HIV), active chronic or acute hepatitis B or C
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent
• Symptomatic ascites or pleural effusion
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study through 180 days after the last dose of study medication
• Major surgery within 16 weeks prior to screening
• Live vaccine within 30 days prior to first dose of study medication

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Geva R, Voskoboynik M, Dobrenkov K, Mayawala K, Gwo J, Wnek R, Chartash E, Long GV. First-in-human phase 1 study of MK-1248, an anti-glucocorticoid-induced tumor necrosis factor receptor agonist monoclonal antibody, as monotherapy or with pembrolizumab in patients with advanced solid tumors. Cancer. 2020 Nov 15;126(22):4926-4935. doi: 10.1002/cncr.33133. Epub 2020 Aug 18.

Reference Type: DERIVED

PMID: 32809217 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-1248-001

Identifier Type: OTHER

Identifier Source: secondary_id

1248-001

Identifier Type: -

Identifier Source: org_study_id