Clinical trial · Interventional
Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC
A Platform Study of RAS(ON) Inhibitors in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)
NCT06162221CI-TRIAL-00116380recruitingPhase 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)
The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other. The first four subprotocols include the following: Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805
Conditions
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| KRAS G12C-mutated Solid Tumors, Lung Cancer | — | UNRESOLVED | — |
| KRAS, NRAS, HRAS-mutated NSCLC | — | UNRESOLVED | — |
| Lung Cancer Stage IV, Advanced Solid Tumor, Cancer | Malignant Lung Neoplasm | CURATED_BROADER | 0.78 |
| Non-Small Cell Lung Cancer, NSCLC | Lung Non-Small Cell Carcinoma | ALIAS | 0.85 |
| RAS G12D-mutated NSCLC | — | UNRESOLVED | — |
Interventions
Interventions (7)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Carboplatin | Drug | Carboplatin | ALIAS |
| Cisplatin | Drug | Cisplatin | ALIAS |
| Pembrolizumab | Drug | Pembrolizumab | ALIAS |
| Pemetrexed | Drug | Pemetrexed | ALIAS |
| RMC-6236 | Drug | — | UNRESOLVED |
| RMC-6291 | Drug | — | UNRESOLVED |
| RMC-9805 | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- Subprotocol A: KRAS G12C-Mutated Solid Tumors
- description
- RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
- interventionNames
- Drug: RMC-6291
- Drug: RMC-6236
- Drug: Pembrolizumab
- Drug: Cisplatin
- Drug: Carboplatin
- Drug: Pemetrexed
- type
- EXPERIMENTAL
- label
- Subprotocol B: RAS-mutated NSCLC
- description
- RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
- interventionNames
- Drug: RMC-6236
- Drug: Pembrolizumab
- Drug: Cisplatin
- Drug: Carboplatin
- Drug: Pemetrexed
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion criteria: All Patients (unless otherwise noted): * ≥ 18 years of age * ECOG PS is 0 to 1 * Adequate organ function as outlined by the study * Received prior standard therapy appropriate for tumor type and stage * Must have pathologically documented, locally advanced or metastatic KRAS G12C-mutated solid tumor malignancy (not amenable to curative surgery) (Subprotocol A) * Must have pathologically documented, locally advanced or metastatic RAS-mutated NSCLC (Subprotocol B) * Must have pathologically documented, locally advanced or metastatic RAS G12D-mutated NSCLC (Subprotocol C and Subprotocol D) Exclusion criteria: All Patients: * Primary central nervous system (CNS) tumors * Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs * Major surgery \< 28 days of first dose * Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids Other inclusion/exclusion criteria may apply.
References
Publications (1)
- DERIVEDCregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J Med Chem. 2025 Mar 27;68(6):6064-6083. doi: 10.1021/acs.jmedchem.4c02314. Epub 2025 Mar 8. PMID 40056080