Clinical trial NCT02553499: Study of MK-1248 With and Without Pembrolizumab (MK-3475) for Participants With Advanced Solid Tumors (MK-1248-001)
Official title: A Phase 1 Trial of MK-1248 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: Solid tumor
PD1
PD-L1
PDL1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-09-17
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
timeFrame: Cycle 1 (Up to 21 days)
Secondary outcomes:
measure: Maximum Concentration (Cmax) of MK-1248 in Serum
timeFrame: At designated timepoints (Up to ~3 months)
measure: Trough Concentration (Ctrough) of MK-1248 in Serum
timeFrame: At designated timepoints (Up to ~3 months)
measure: Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) of MK-1248 in Serum
timeFrame: At designated timepoints (Up to ~3 months)
measure: Maximum Concentration (Cmax) of Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) Receptor Target Engagement
timeFrame: At designated timepoints (Up to ~4.5 months)
measure: Trough (Minimum) Concentration (Ctrough) of Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) Receptor Target Engagement
timeFrame: At designated timepoints (Up to ~4.5 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.