Overview
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
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: 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
- 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