Clinical trial · Interventional
Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014)
Phase 1b Open-label Study of MK-8353 in Combination With Selumetinib (MK-5618) in Participants With Advanced/Metastatic Solid Tumors
NCT03745989CI-TRIAL-00068270completedPhase 1Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is a multicenter, worldwide, open-label study of MK-8353 in combination with selumetinib in participants with histologically or cytologically confirmed diagnosis of advanced solid tumor. This study will evaluate the safety, tolerability, and exploratory efficacy of MK-8353 in combination with selumetinib.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Solid Tumors | Solid Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| MK-8353 | Drug | — | UNRESOLVED |
| Selumetinib | Drug | Selumetinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- MK-8353 and Selumetinib Dose Escalation
- description
- Participants will receive a combination MK-8353 and selumetinib for 4 days on and 3 days off until disease progression or discontinuation. MK-8353 will be escalated sequentially from 50 mg to 250 mg based on pharmacokinetic and safety data. Selumetinib will be escalated sequentially from 25 mg to 75 mg based on pharmacokinetic and safety data. Doses may be adjusted downward sequentially based on tolerability
- interventionNames
- Drug: MK-8353
- Drug: Selumetinib
Primary outcomes (3)
- measure
- Number of Participants Experiencing Dose Limiting Toxicities
- timeFrame
- Cycle 1 (3-week Cycle) (Up to 3 weeks)
- description
- A dose limiting toxicity (DLT) is defined as any hematologic or non-hematologic toxicity ≥Grade 3 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The occurrence of any of the designated toxicities during Cycle 1 (3-week cycle) were considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration. The number of participants experiencing DLTs was assessed.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Have a histologically- or cytologically-documented, locally-advanced or metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit. * Provide an archival or newly obtained tumor tissue sample and blood samples for assessment of proto-oncogene rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF) mutation and for biomarker analysis. * Have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) on imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) as assessed by the investigator/local radiology review. * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. (Obtain within 7 days prior to first dose of study treatment.) * Have the ability to swallow and retain oral medication. * Demonstrate adequate organ function. * Male participants must agree to use an acceptable contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. * Female participants must not be pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the study's contraceptive guidance during the treatment period and for at least 120 days, after the last dose of study intervention. Exclusion Criteria: * Have had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study treatment, or has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related AEs). * Have clinically active central nervous system metastases and/or carcinomatous meningitis. * Have an active infection requiring therapy. * Have known human immunodeficiency virus (HIV) and/or Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA). * Have clinically significant cardiovascular disease as defined by study criteria. * Have a history of thromboembolic or cerebrovascular events within 6 months prior to treatment start, including transient ischemic attacks (TIAs), cerebrovascular accidents (CVAs), deep vein thrombosis, or pulmonary embolism. * Have neuromuscular disorders associated with an elevated creatine kinase (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). * Have one or more study-defined ophthalmological findings/conditions. * Have a known history of Gilbert's Syndrome. * Have a history or current evidence of a gastrointestinal (GI) condition (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications. * Have a known psychiatric or substance abuse disorder, or any other cognitive disorder that would interfere with the participant's ability to cooperate with the requirements of the study. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study treatment. * Received prior therapy with a mitogen activated protein kinase (MEK) inhibitor (e.g., cobimetinib, trametinib), or an extracellular signal-regulated kinase (ERK) inhibitor (e.g., MK-8353, GCD-0994, ulixertinib), or a proto-oncogene BRAF inhibitor (e.g., dabrafenib, vemurafenib). * Is 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 of administration of selumetinib. * Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents and/or excipients used in the study. * A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
References
Publications (1)
- RESULTStathis A, Tolcher AW, Wang JS, Renouf DJ, Chen LC, Suttner LH, Freshwater T, Webber AL, Nayak T, Siu LL. Results of an open-label phase 1b study of the ERK inhibitor MK-8353 plus the MEK inhibitor selumetinib in patients with advanced or metastatic solid tumors. Invest New Drugs. 2023 Jun;41(3):380-390. doi: 10.1007/s10637-022-01326-3. Epub 2023 Apr 11. PMID 37040046