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

Launched by MERCK SHARP & DOHME LLC · Oct 1, 2021

Keywords

ClinConnect Summary

This clinical trial, titled "A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors," is investigating a new treatment called MK-1084 for patients with advanced solid tumors that have a specific genetic mutation known as KRAS G12C. The study aims to see how safe the treatment is, how the body processes it, and whether it is effective on its own or when combined with other therapies. The trial is currently recruiting participants aged 65 and older, regardless of gender, who have measurable disease and good organ function.

To join the study, participants should have advanced cancers that have already been treated at least once or have untreated non-small cell lung cancer with specific characteristics. During the trial, participants will receive MK-1084 and will be monitored closely to track any side effects and how well the treatment works. It's important for potential participants to understand the eligibility criteria, as some health conditions may prevent them from joining. Overall, this trial is a promising opportunity for patients with challenging cancer types to access new treatments.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• For all participants:
• • Has measurable disease by RECIST 1.1 criteria
• • Has adequate organ function
• • Male participants agree to protocol-specified contraception requirements including refraining from donating sperm and using protocol-specified contraceptives unless confirmed to be azoospermic
• • Female participants must not be pregnant or breastfeeding, and must agree to protocol-specified contraceptive requirements 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 and submits archival tumor sample
• • 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