Clinical trial · Interventional
Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
NCT05379985CI-TRIAL-00111795recruitingPhase 1 / Phase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.
Conditions
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Solid Tumors | Solid Neoplasm | CURATED_BROADER | 0.80 |
| Colorectal Cancer (CRC) | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
| Non-small Cell Lung Cancer (NSCLC) | Lung Non-Small Cell Carcinoma | ALIAS | 0.85 |
| Pancreatic Ductal Adenocarcinoma (PDAC) | Pancreatic Ductal Adenocarcinoma | ONTOLOGY_EXACT | 0.85 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| RMC-6236 | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Experimental: RMC-6236
- description
- 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)
- interventionNames
- Drug: RMC-6236
Primary outcomes (2)
- measure
- Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs
- timeFrame
- up to 2.5 years
- measure
- Number of Participants with Dose-Limiting Toxicity (DLT)
- timeFrame
- 21 days
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (5)
- DERIVEDArbour KC, Punekar S, Luo J, Johnson M, Spira A, Herzberg B, Starodub A, Sommerhalder D, Hecht JR, Garrido-Laguna I, Barve M, Ou SI, Kar S, Bao L, Tao L, Vora R, Hegde A, Saltos A, Azad NS, Hong DS; RMC-6236-001 Investigators. Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2026 Sep 3;395(9):882-893. doi: 10.1056/NEJMoa2504059. PMID 42685317
- DERIVEDWolpin 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
- DERIVEDJiang 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 Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers. Cancer Discov. 2024 Jun 3;14(6):994-1017. doi: 10.1158/2159-8290.CD-24-0027. PMID 38593348
- DERIVEDHolderfield 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, Lito P, Santamaria D, Aguirre AJ, Waters AM, Der CJ, Ambrogio C, Wang Z, Gill AL, Koltun ES, Smith JAM, Wildes D, Singh M. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Nature. 2024 May;629(8013):919-926. doi: 10.1038/s41586-024-07205-6. Epub 2024 Apr 8. PMID 38589574
- DERIVEDSchulze 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 of a cellular chaperone to target the active state of mutant KRAS. Science. 2023 Aug 18;381(6659):794-799. doi: 10.1126/science.adg9652. Epub 2023 Aug 17.