MK-1084: This phase I trial is evaluating how safe and effective targeted therapy (MK-1084) is alone in people with advanced solid cancers with KRASG12C mutation, and when it is combined with immunotherapy (pembrolizumab) in people with non-small cell cancer with KRASG12C mutationA Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-1084 as Monotherapy and in Combination With Pembrolizumab in Subjects With KRASG12C Mutant Advanced Solid Tumors

Inclusion

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: 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

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

- Untreated locally advanced unresectable or metastatic colorectal adenocarcinoma with histologically or blood-based confirmation of KRAS G12C mutation