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

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 preferredand usual lifestyle (abstinent on a long-term and persistent basis) and agree toremain abstinent OR must agree to use contraception unless confirmed to beazoospermic

• Female participants must not be pregnant or breastfeeding, and at least one of thefollowing conditions applies: is not a woman of child-bearing potential (WOCBP); isa WOCBP and uses a contraceptive method that is highly effective, with low userdependency, or be abstinent from heterosexual intercourse as their preferred andusual lifestyle and must have a negative highly sensitive pregnancy test within 24hours (for a urine test) or 72 hours (for a serum test) before the first dose ofstudy 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 histologicallyOR blood-based confirmation of KRAS G12C mutation and histologic confirmation ofprogrammed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%

For Arm 3

• Has locally advanced unresectable or metastatic solid-tumor malignancy withhistologically or blood-based confirmation of KRAS G12C mutation who has received atleast 1 line of therapy for systemic disease Expansion Group A: 3L/4L metastaticcolorectal cancer (mCRC)

• Has histologically or cytologically confirmed diagnosis of unresectable andmetastatic colorectal adenocarcinoma with histological or blood-based confirmationof KRAS G12C mutation

• Previous treatment failure of 2 or 3 previous lines of systemic therapy ExpansionGroup B

• Has locally advanced unresectable or metastatic solid-tumor malignancy, excludingNSCLC or CRC, with histologically or blood- based confirmation of KRAS G12C mutationwho 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 unresectableor metastatic colorectal adenocarcinoma and with histologically or blood-basedconfirmation 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 withhistologically 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 beencompleted with no evidence of malignancy for 5 years

• Has clinically active central nervous system (CNS) metastases and/or carcinomatousmeningitis

• Has an active infection requiring systemic therapy

• Known history of HIV infection or. has a known history of Hepatitis B virus or knownactive Hepatitis C virus infection

• Has a history of interstitial lung disease, noninfectious pneumonitis requiringactive steroid therapy, or ongoing pneumonitis

• Has an active autoimmune disease requiring systemic therapy

• Has not fully recovered from any effects of major surgical procedure withoutsignificant detectable infection

• Has one or more of the following ophthalmological findings/conditions: intraocularpressure >21 mm Hg and/or any diagnosis of glaucoma; diagnosis of central serousretinopathy, retinal vein occlusion, or retinal artery occlusion and/or a diagnosisof 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 forlong-acting agents [for example, piroxicam]) before, during, and for at least 2 daysafter administration of pemetrexed.

• Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone