Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Brief summary public domain (ClinicalTrials.gov)

Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.

Detailed description public domain (ClinicalTrials.gov)

This is a Phase 1/2, multicenter open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of escalating doses of RMC-6236 in adult patients with advanced solid tumors harboring specific RAS mutations, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose \[RP2D\] within investigated patient population groups. RMC-6236 is a potent, orally bioavailable RAS-MULTI(ON) inhibitor, selective for the active RAS(ON) form of both wild type and mutant variants of the canonical RAS isoforms (HRAS, NRAS, and KRAS).

Intervention public domain (ClinicalTrials.gov)

Drug: RMC-6236. Oral Tablets

Arm public domain (ClinicalTrials.gov)

Experimental: RMC-6236 (experimental): Enrollment into dose exploration may be from any advanced solid tumor type with KRAS p.G12 mutations. Enrollment into dose expansion/optimization may be from groups consisting of patients with a single histotype/genotype (for example, KRAS G12-mutated NSCLC, PDAC, CRC, RAS mutant NSCLC, Melanoma, gynecological cancer or other solid tumors not previously specified). RAS mutant is defined as any nonsynonymous mutation of KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61)

Primary outcome public domain (ClinicalTrials.gov)

Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs. Time frame: up to 2.5 years.

Primary outcome public domain (ClinicalTrials.gov)

Number of Participants with Dose-Limiting Toxicity (DLT). Time frame: 21 days.

Secondary outcome public domain (ClinicalTrials.gov)

Maximum Observed Blood Concentration (Cmax) of RMC-6236. Time frame: up to 15 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236. Time frame: up to 15 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Area Under Blood Concentration Time Curve (AUC) of RMC-6236. Time frame: up to 15 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Elimination Half-Life of RMC-6236 (t1/2). Time frame: up to 15 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing. Time frame: up to 15 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Overall Response Rate (ORR). Time frame: up to 2.5 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing. PDAC with wild-type RAS (expansion). * Treatment naive or have received prior standard therapy appropriate for tumor type and stage * Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ function Exclusion Criteria: * Primary central nervous system (CNS) tumors * Active, untreated brain metastases * Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication * History of any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy Other inclusion/exclusion criteria may apply.

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 754 participants (estimated).