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

Official title

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

Overview

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

Detailed description

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).

Interventions

• Drug RMC-6236
  Oral Tablets

Primary outcome measures

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

Secondary outcome measures (10)

• Maximum Observed Blood Concentration (Cmax) of RMC-6236 [Time frame: up to 15 weeks]
• Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236 [Time frame: up to 15 weeks]
• Area Under Blood Concentration Time Curve (AUC) of RMC-6236 [Time frame: up to 15 weeks]
• Elimination Half-Life of RMC-6236 (t1/2) [Time frame: up to 15 weeks]
• Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing [Time frame: up to 15 weeks]
• Overall Response Rate (ORR) [Time frame: up to 2.5 years]
• Duration of Response (DOR) [Time frame: up to 2.5 years]
• Disease Control Rate (DCR) [Time frame: up to 2.5 years]
• Time to Response (TTR) [Time frame: up to 2.5 years]
• Progression-Free Survival (PFS) [Time frame: up to 2.5 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 21 centers

• UC Irvine/Chao Family Comprehensive Cancer Center — Orange
• UCLA — Santa Monica
• Moffitt Cancer Center — Tampa
• Piedmont Healthcare — Atlanta
• Mary Bird Perkins Cancer Center — Baton Rouge
• Johns Hopkins University — Baltimore
• Dana Farber Cancer Institute — Boston
• Perlmutter Cancer Center at NYU Langone Health — New York
• … and 13 more centers

Publications

• Wolpin BM, Park W, Garrido-Laguna I, Spira A, Starodub A, Sommerhalder D, Punekar SR, Barve M, Pelster M, Herzberg B, Azad NS, Hecht JR, Ou SHI, Lin T, Kar S, Tao L, Vora R, Hegde A, Aung K, Hong DS; RMC-6236-001 Investigators. Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer. N Engl J Med. 2026 May 7;394(18):1790-1802. doi: 10.1056/NEJMoa2505783. PMID 42090791
• Jiang J, Jiang L, Maldonato BJ, Wang Y, Holderfield M, Aronchik I, Winters IP, Salman Z, Blaj C, Menard M, Brodbeck J, Chen Z, Wei X, Rosen MJ, Gindin Y, Lee BJ, Evans JW, Chang S, Wang Z, Seamon KJ, Parsons D, Cregg J, Marquez A, Tomlinson ACA, Yano JK, Knox JE, Quintana E, Aguirre AJ, Arbour KC, Reed A, Gustafson WC, Gill AL, Koltun ES, Wildes D, Smith JAM, Wang Z, Singh M. Translational and The PMID 38593348
• Holderfield M, Lee BJ, Jiang J, Tomlinson A, Seamon KJ, Mira A, Patrucco E, Goodhart G, Dilly J, Gindin Y, Dinglasan N, Wang Y, Lai LP, Cai S, Jiang L, Nasholm N, Shifrin N, Blaj C, Shah H, Evans JW, Montazer N, Lai O, Shi J, Ahler E, Quintana E, Chang S, Salvador A, Marquez A, Cregg J, Liu Y, Milin A, Chen A, Ziv TB, Parsons D, Knox JE, Klomp JE, Roth J, Rees M, Ronan M, Cuevas-Navarro A, Hu F, L PMID 38589574
• Schulze CJ, Seamon KJ, Zhao Y, Yang YC, Cregg J, Kim D, Tomlinson A, Choy TJ, Wang Z, Sang B, Pourfarjam Y, Lucas J, Cuevas-Navarro A, Ayala-Santos C, Vides A, Li C, Marquez A, Zhong M, Vemulapalli V, Weller C, Gould A, Whalen DM, Salvador A, Milin A, Saldajeno-Concar M, Dinglasan N, Chen A, Evans J, Knox JE, Koltun ES, Singh M, Nichols R, Wildes D, Gill AL, Smith JAM, Lito P. Chemical remodeling PMID 37590355

Identifiers

NCT: NCT05379985 · RMC-6236-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗