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

NCT02553499 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 1248-001MK-1248-001
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

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

Keywords

Solid tumor; PD1; PD-L1; PDL1

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)

  The occurrence of any of the following toxicities during Cycle 1 (21 days), if possibly, probably or definitely related to study treatment, was considered a DLT: 1. Grade 4 non-hematological toxicity 2. Grade 4 hematological toxicity lasting \>7 days, except thrombocytopenia a. Grade 4 thrombocytopenia of any duration b. Grade 3 thrombocytopenia is a DLT if associated with bleeding 3. Any Grade 3 non-hematological toxicity, with the exceptions 4. Any Grade 3 or Grade 4 non-hematological laboratory abnormality, if medical intervention was required, or abnormality led to hospitalization, or abnormality persisted for \>1 week 5. Febrile neutropenia Grade 3 or Grade 4 6. Any drug-related AE which caused participant to discontinue study treatment during Cycle 1 7. Grade 5 toxicity 8. Any treatment-related toxicity which caused a \>2-week delay in initiation of Cycle 2.

  Cycle 1 (Up to 21 days)

Secondary Outcomes (5)

• Maximum Concentration (Cmax) of MK-1248 in Serum

  At designated timepoints (Up to ~3 months)

• Trough Concentration (Ctrough) of MK-1248 in Serum

  At designated timepoints (Up to ~3 months)

• Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) of MK-1248 in Serum

  At designated timepoints (Up to ~3 months)

• Maximum Concentration (Cmax) of Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) Receptor Target Engagement

  At designated timepoints (Up to ~4.5 months)

• Trough (Minimum) Concentration (Ctrough) of Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) Receptor Target Engagement

  At designated timepoints (Up to ~4.5 months)

Study Arms (2)

MK-1248

EXPERIMENTAL

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).

Biological: MK-1248

MK-1248 + Pembrolizumab

EXPERIMENTAL

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).

Biological: MK-1248; Biological: pembrolizumab

Interventions

MK-1248 BIOLOGICAL

IV infusion

MK-1248; MK-1248 + Pembrolizumab

pembrolizumab BIOLOGICAL

IV infusion

Also known as: KEYTRUDA®, MK-3475

MK-1248 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 32809217 DERIVED

MeSH Terms

Interventions

pembrolizumab

Limitations and Caveats

Enrollment into this study was prematurely discontinued due to program prioritization and not related to any safety concerns.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: September 17, 2015
• Study Start: November 12, 2015
• Primary Completion: October 17, 2018
• Study Completion: October 17, 2018
• Last Updated: November 4, 2019
• Results First Posted: November 4, 2019

Record last verified: 2019-10