RecruitingPhase 1NCT05067283
A Study of Calderasib (MK-1084) in KRAS Mutant Advanced Solid Tumors (MK-1084-001)
A Phase 1, Open-label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-1084 as Monotherapy and as Part of Various Combination Therapies in Participants With KRAS G12C Mutant Advanced Solid Tumors
Sponsor
Merck Sharp & Dohme LLC
Enrollment
830 participants
Start Date
Dec 17, 2021
Study Type
INTERVENTIONAL
Conditions
Summary
This is a study evaluating the safety, pharmacokinetics, and efficacy of calderasib alone, and calderasib plus other combination therapies in participants with advanced solid tumors with identified kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation.
Eligibility
Min Age: 18 Years
Inclusion Criteria19
- For all participants:
- Has measurable disease by RECIST 1.1 criteria
- Has adequate organ function
- Male participants agree to protocol-specified contraception requirements including refraining from donating sperm and using protocol-specified contraceptives unless confirmed to be azoospermic
- Female participants must not be pregnant or breastfeeding, and must agree to protocol-specified contraceptive requirements and must have a negative highly sensitive pregnancy test within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention
- For Arm 1 - Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically OR blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease
- For Arm 2
- \- Has an untreated metastatic non-small cell lung cancer (NSCLC) with histologically OR blood-based confirmation of KRAS G12C mutation and histologic confirmation of programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%
- For Arm 3
- Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically or blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease Expansion Group A: 2L+NSCLC
- Has histologically or cytologically confirmed diagnosis of unresectable or metastatic NSCLC with histological or blood-based confirmation of KRAS G12C mutation and submits archival tumor sample
- Previous treatment failure of at least 1 line of systemic therapy Expansion Group B
- Has locally advanced unresectable or metastatic solid-tumor malignancy, excluding NSCLC or CRC, with histologically or blood- based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease
- Arm 4 only - Has an untreated advanced or metastatic nonsquamous NSCLC with histologically or blood-based confirmation of KRAS G12C mutation
- Arm 5 only
- Histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic colorectal adenocarcinoma and with histologically or blood-based confirmation of KRAS G12C mutation
- Previous treatment failure of one or 2 previous line(s) of systemic therapy
- Arm 6 only
- \- Locally advanced unresectable or metastatic colorectal adenocarcinoma with histologically or blood-based confirmation of KRAS G12C mutation
Exclusion Criteria13
- Has received chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before first dose of study intervention
- Has a history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 5 years
- Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active infection requiring systemic therapy
- Known history of HIV infection or. has a known history of Hepatitis B virus or known active Hepatitis C virus infection
- Has a history of interstitial lung disease, noninfectious pneumonitis requiring active steroid therapy, or ongoing pneumonitis
- Has an active autoimmune disease requiring systemic therapy
- Has not fully recovered from any effects of major surgical procedure without significant detectable infection
- Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mm Hg and/or any diagnosis of glaucoma; diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and/or a diagnosis of retinal degenerative disease
- Has received live or live-attenuated vaccine within 4 weeks of study start
- Arm 4 Only
- Is unable to interrupt aspirin or other nonsteroidal anti-inflammatories (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents \[for example, piroxicam\]) before, during, and for at least 2 days after administration of pemetrexed.
- Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone
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Interventions
DRUGCalderasib
Oral dose
BIOLOGICALPembrolizumab
Intravenous infusion of 200 mg
DRUGcarboplatin
Per label
DRUGpemetrexed
Per label
BIOLOGICALcetuximab
Per label
DRUGoxaliplatin
Per label
DRUGleucovorin
Per label
DRUG5-fluorouracil
Per label
Locations(73)
View Full Details on ClinicalTrials.gov
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NCT05067283
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