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

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

Detailed Description
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This is a Phase 1/1b, 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).

Official Title
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A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Conditions
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Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors

Intervention / Treatment
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* Drug: RMC-6236


Participation Criteria
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Eligibility Criteria
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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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: RMC-6236<br>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, PDAC, CRC, 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) | Drug: RMC-6236<br>* Oral Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs |  | up to 2.5 years | 
| Number of Participants with Dose-Limiting Toxicity (DLT) |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Blood Concentration (Cmax) of RMC-6236 |  | up to 15 weeks | 
| Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236 |  | up to 15 weeks | 
| Area Under Blood Concentration Time Curve (AUC) of RMC-6236 |  | up to 15 weeks | 
| Elimination Half-Life of RMC-6236 (t1/2) |  | up to 15 weeks | 
| Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing |  | up to 15 weeks | 
| Overall Response Rate (ORR) | Overall response rate per RECIST v1.1 | up to 2.5 years | 
| Duration of Response (DOR) | Duration of response per RECIST v1.1 | up to 2.5 years | 
| Disease Control Rate (DCR) | Disease control rate per RECIST v1.1 | up to 2.5 years | 
| Time to Response (TTR) | Time to response per RECIST v1.1 | up to 2.5 years | 
| Progression-Free Survival (PFS) | Progression-free survival per RECIST v1.1 | up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Cancer, Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, NSCLC, CRC, PDAC, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Colorectal Neoplasms, Colonic Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Lung Neoplasms, KRAS, Non-small Cell Lung Cancer, Lung Cancer, Colorectal Cancer, Colon Cancer, Carcinoma, Non-Small-Cell Lung, Neoplastic Processes, Thoracic Neoplasms, Antineoplastic Agents, Melanoma, Gynecological Cancers, RAS