Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001)

Completed · Phase 1

Conditions studied: Neoplasms

In brief

This study consists of several parts: dose escalation, dose expansion, dose expansion in Chinese participants residing in China, and coformulation. Dose escalation is to evaluate the safety, tolerability, and preliminary efficacy of MK-4830 monotherapy administration (Arms A and B) and in combination with pembrolizumab (Arm C). Dose expansion is to evaluate the objective response rate (ORR) of MK-4830 in combination with pembrolizumab (Arms A-F); evaluate the safety and tolerability of MK-4830 administered in combination with pembrolizumab, carboplatin, and pemetrexed (Arm G) and of MK-4830 administered in combination with pembrolizumab and lenvatinib (Arm H); evaluate the safety, tolerability and ORR of MK-4830 in combination with pembrolizumab plus chemotherapy (Arms I-L); and evaluate the safety and tolerability of MK-4830 in combination with pembrolizumab in Chinese participants from China (Arm M). The coformulation part (Arm N) evaluates the safety and tolerability of MK-4830A (coformulation of MK-4830 800 mg + pembrolizumab 200 mg). There is no formal hypothesis testing in this study.

Key facts

Study ID

NCT03564691

Run by

Merck Sharp & Dohme LLC

People needed

470

Starts

2018-07-11

Expected to finish

2025-09-26

Last updated by the study team

2025-10-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Dose escalation participants: Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and has received, has been intolerant to, or has been ineligible for all treatment known to confer clinical benefit. Solid tumors of any type are eligible for enrollment
• Has measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), Response Assessment in Neuro-Oncology (RANO), or modified RECIST (mRECIST) as assessed by the local site investigator/radiology
• Submits an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample). This inclusion criterion does not apply to Expansion phase Arm M
• Dose Escalation Part C and Back-fill participants: Has 1 or more discrete malignant lesions that are amenable to biopsy
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. This inclusion criterion does not apply to Expansion phase Arm B
• Demonstrates adequate organ function
• A male participant must agree to use an approved contraception(s) during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) OR if a WOCBP agrees to follow the study contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment
• Expansion phase Arm A participants:
• Has histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
• Received at least 1 prior line of therapy and no more than 3 prior lines of systemic therapy
• Expansion phase Arm B participants:
• Has histologically or cytologically confirmed unresectable glioblastoma multiforme (GBM) or its variants
• Has a Karnofsky performance status (KPS) ≥ 70
• Has had no more than 1 prior line of therapy for GBM. Radiation with or without chemotherapy is acceptable as the prior treatment
• Has shown unequivocal evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan by contrast within 2 weeks prior to randomization
• Has an interval of at least 3 weeks (to randomization) between prior surgical resection (one week for stereotactic biopsy)
• Has an interval of at least 12 weeks from the completion of radiation therapy to randomization unless there is unequivocal histologic confirmation of tumor progression or radiographic progression outside of the prior radiation field
• Is neurologically stable (eg, without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable
• Expansion phase Arm C participants:
• Has histologically confirmed recurrent or metastatic head and neck squamous cell cancer (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
• Has experienced disease progression at any time during or after treatment with a platinum-containing (eg, carboplatin or cisplatin) regimen with or without cetuximab
• Expansion phase Arm D participants:
• Has histologically confirmed advanced or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
• Has not had any prior programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) therapy

You may not qualify if…

• Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier
• Has not recovered from all radiation-related toxicities to Grade 1 or less, requires corticosteroids, and had radiation pneumonitis
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Has known untreated central nervous system metastases or known carcinomatous meningitis. This exclusion criterion does not apply to Expansion phase Arm B
• Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related AEs
• Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of pembrolizumab and/or chemotherapy agents
• Has an active infection requiring therapy
• Has a history or current interstitial lung disease
• Has a history of noninfectious pneumonitis that required steroids or current pneumonitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure
• Has a known history of human immunodeficiency virus (HIV)
• Has a known active hepatitis B or C
• Is taking chronic systemic steroids in doses >10 mg daily of prednisone or equivalent within 7 days prior to the first dose of trial treatment
• Has not fully recovered from any effects of major surgery without significant detectable infection. Surgical proceduress that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered
• Has received a live or live-attenuated virus vaccine within 30 days prior to first dose of study intervention
• Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of MK-4830
• All Expansion phase participants:
• Tumor types with known MSI-high status are not eligible
• Expansion phase Arm A participants:
• Has received more than 3 lines of prior therapy for advanced disease (pancreatic cancer)
• Expansion phase Arm B participants:
• Has tumor primarily localized to the brainstem or spinal cord
• Has presence of diffuse leptomeningeal disease or extracranial disease
• Has recurrent tumor greater than 6 cm in maximum diameter

Where it is running

• University of California at San Francisco ( Site 0004) — San Francisco, California, United States
• Henry Ford Health System ( Site 0002) — Detroit, Michigan, United States
• Washington University ( Site 0003) — St Louis, Missouri, United States
• John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005) — Hackensack, New Jersey, United States
• Laura and Isaac Perlmutter Cancer Center ( Site 0008) — New York, New York, United States
• Ohio State University Arthur G James Cancer Hospital & Richard J Solove Research Institute ( Site 00 — Columbus, Ohio, United States
• South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001) — San Antonio, Texas, United States
• Utah Cancer Specialists ( Site 0011) — Salt Lake City, Utah, United States
• Seattle Cancer Care Alliance ( Site 0010) — Seattle, Washington, United States
• Liverpool Hospital-Medical Oncology ( Site 0250) — Liverpool, New South Wales, Australia
• Princess Alexandra Hospital ( Site 0253) — Brisbane, Queensland, Australia
• Juravinski Cancer Centre ( Site 0034) — Hamilton, Ontario, Canada
• The Ottawa Hospital ( Site 0031) — Ottawa, Ontario, Canada
• Princess Margaret Cancer Centre ( Site 0033) — Toronto, Ontario, Canada
• The First Hospital of Jilin University ( Site 0803) — Changchun, Jilin, China
• Shanghai Chest Hospital-Oncology department ( Site 0801) — Shanghai, Shanghai Municipality, China
• West China Hospital of Sichuan University ( Site 0804) — Chengdu, Sichuan, China
• Centre Oscar Lambret ( Site 2002) — Lille, Nord, France
• Centre Hospitalier Universitaire de Poitiers ( Site 2000) — Poitiers, Vienne, France
• Hôpital Européen Georges Pompidou ( Site 2003) — Paris, Île-de-France Region, France
• University General Hospital of Heraklion ( Site 0110) — Heraklion, Irakleio, Greece
• Euromedica General Clinic of Thessaloniki-Oncology Unit ( Site 0112) — Thessaloniki, Greece
• European Interbalkan Medical Center ( Site 0111) — Thessaloniki, Greece
• Rambam Health Care Campus-Oncology Division ( Site 0042) — Haifa, Israel
• Rabin Medical Center ( Site 0043) — Petah Tikva, Israel

Full record on ClinicalTrials.gov

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