a study of mk-1084 in kras mutant advanced solid tumors (mk-1084-001)

Conditions: Advanced Solid Tumors

Summary: this is a study evaluating the safety, pharmacokinetics, and efficacy of mk-1084 alone, and mk-1084 plus other combination therapies in participants with advanced solid tumors with identified kirsten rat sarcoma viral oncogene homolog g12c (kras g12c) mutation.


Eligibility criteria:
inclusion criteria: for all participants: * has measurable disease by recist 1.1 criteria * has adequate organ function * male participants must be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception unless confirmed to be azoospermic * female participants must not be pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of child-bearing potential (wocbp); is a wocbp and uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle 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 * 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 criteria: * 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