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

Официальное название

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

Обзор

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

Подробное описание

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).

Вмешательства

• Препарат RMC-6236
  Oral Tablets

Первичные конечные точки

• Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs [Срок оценки: up to 2.5 years]
• Number of Participants with Dose-Limiting Toxicity (DLT) [Срок оценки: 21 days]

Вторичные конечные точки (10)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 21 центр

• 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
• … и ещё 13 центров

Публикации

• 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

Идентификаторы

NCT: NCT05379985 · RMC-6236-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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