Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001)

• Status: Recruiting
• Trial end date: 2024-10-25
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the safety and pharmacokinetics of MK-5890 when administered alone and in combination with pembrolizumab (MK-3475) in adults with advanced solid tumors. The initial course of MK-5890 monotherapy or MK-5890 plus pembrolizumab combination therapy will be for up to 35 administrations (approximately 2 years). The safety and pharmacokinetics of MK-5890 when administered with pembrolizumab, pemetrexed and carboplatin in adults with nonsquamous non-small cell lung cancer (NSCLC) and MK-5890 when administered with pembrolizumab and nab-paclitaxel in adults with triple-negative breast cancer (TNBC) will also be assessed.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Carboplatin; Paclitaxel; Pembrolizumab; Pemetrexed

Criteria

Inclusion Criteria:

• Arms 1 & 2: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and has received or been intolerant to all treatment known to confer clinical benefit

• Arm 3: Histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per current American Joint Committee on Cancer criteria) nonsquamous NSCLC

• Arm 4: Triple-negative breast cancer (TNBC) that is locally recurrent, inoperable, not previously treated with chemotherapy, and which cannot be treated with curative intent OR metastatic disease not previously treated with chemotherapy

• Measureable disease by RECIST 1.1. as assessed by the local site investigator/radiologist. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions

• Adequate organ function

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Male participants must agree to use adequate contraception during the treatment period and for at least 120 days after the last dose of MK-5890 or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents and refrain from donating sperm during this period

• Female participants must not be pregnant or breastfeeding and agree to follow use adequate contraception during the treatment period and for at least 120 days after the last dose of MK-5890 or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents

• Submit an evaluable baseline tumor sample for analysis (either a newly obtained or archival tumor sample)

Exclusion Criteria:

• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years

• Clinically active central nervous system metastases and/or carcinomatous meningitis

• Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or other components of the study treatment

• Active infection requiring systemic treatment

• History of interstitial lung disease

• History of (noninfectious) pneumonitis that required steroids or current pneumonitis

• Symptomatic ascites or pleural effusion

• Previously had a stem cell or bone marrow transplant

• Previously had a solid organ transplant

• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy

• Known human immunodeficiency virus (HIV) and/or active and acute Hepatitis B or C infections

• Not fully recovered from any effects of major surgery without significant detectable infection

• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study

• Had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study treatment, or has not recovered to Grade ≤1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier

• Expected to require any other form of antineoplastic therapy while participating in this study

• On chronic systemic steroid therapy in excess of replacement doses (e.g., exceeding 10 mg/day of prednisone equivalent), or on any other form of immunosuppressive medication

• Regular user (including "recreational use") of any illicit drugs at the time of signing informed consent, or has a recent history (within the last year) of substance abuse (including alcohol), as determined by the treating investigator. Participants who use cannabis for medicinal purposes or to treat specific symptoms will not be excluded unless it is being abused in the opinion of the treating investigator

• Received a live-virus vaccine within 28 days before the first dose of study treatment

• Currently participating and receiving study treatment in a study of an investigational agent or has participated and received study treatment in a study of an investigational agent or has used an investigational device within 28 days before the first dose of study treatment

Additional Exclusion Criteria for Participants in Arm 3:

• Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months before the first dose of study treatment

• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).

• Is unable or unwilling to take folic acid or vitamin B12 supplementation

Additional Exclusion Criteria for Participants in Arm 4:

• Has a known history of hypersensitivity or allergy to nab-paclitaxel or any of its components

• Has neuropathy ≥Grade 2

• Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization

• Has received previous treatment with immune checkpoint inhibitor(s) (eg, Programmed Cell Death Receptor 1 (PD-1)/PD-L1)