A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)

Eligibility Criteria

• * 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
• * 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: 3L/4L metastatic colorectal cancer (mCRC)
• * Has histologically or cytologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma with histological or blood-based confirmation of KRAS G12C mutation
• * Previous treatment failure of 2 or 3 previous lines 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
• * 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
• * 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
• * 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