RMC-6236

DRUG8 trials

Sponsors

Revolution Medicines Inc., Revolution Medicines, Inc., Amgen, Tango Therapeutics, Inc.

Conditions

Advanced Gastrointestinal, Biliary Tract, and Pancreatic CancersAdvanced Solid TumorsCRCColorectal CancerColorectal Cancer (CRC)Gastrointestinal CancerKRAS G12C-mutated Solid Tumors, Lung CancerKRAS, NRAS, HRAS-mutated NSCLC

Phase 1

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

RecruitingNCT05379985

Revolution Medicines, Inc.Advanced Solid Tumors, Colorectal Cancer (CRC), Non-small Cell Lung Cancer (NSCLC) +1

Start: 2022-05-31End: 2027-07-26Target: 754Updated: 2025-11-12

Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors

RecruitingNCT06040541

Revolution Medicines, Inc.Advanced Solid Tumors, Colorectal Cancer (CRC), Non-small Cell Lung Cancer (NSCLC) +1

Start: 2023-09-07End: 2027-04-30Target: 604Updated: 2025-08-28

Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC

RecruitingNCT06162221

Revolution Medicines, Inc.KRAS G12C-mutated Solid Tumors, Lung Cancer, KRAS, NRAS, HRAS-mutated NSCLC, Lung Cancer Stage IV, Advanced Solid Tumor, Cancer +2

Start: 2024-01-18End: 2028-12-01Target: 616Updated: 2026-03-09

A Study Evaluating Anvumetostat in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103)

RecruitingNCT06360354

AmgenAdvanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers

Start: 2024-05-29End: 2029-02-25Target: 350Updated: 2026-03-31

Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors

RecruitingNCT06445062

Revolution Medicines, Inc.Colorectal Cancer, CRC, Gastrointestinal Cancer +3

Start: 2024-05-24End: 2027-07-15Target: 1130Updated: 2026-04-01

Study of RMC-6291, With or Without RMC-6236, in Combination With Other Anti-Cancer Agents, in Patients With RAS G12C-Mutated Non-Small Cell Lung Cancer – Subprotocol A

RecruitingCTIS2023-509571-16-00

Revolution Medicines Inc.Lung Cancer

Start: 2024-07-17Target: 162Updated: 2025-12-17

Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients

RecruitingNCT06922591

Tango Therapeutics, Inc.Lung Cancer, MTAP Deletion, NSCLC +5

Start: 2025-05-31End: 2027-12-31Target: 183Updated: 2025-12-11

Phase 3

Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

Active, not recruitingNCT06625320

Revolution Medicines, Inc.Pancreatic Cancer, PDAC, PDAC - Pancreatic Ductal Adenocarcinoma

Start: 2024-10-16End: 2027-12-31Updated: 2025-12-12

Related Papers

Abstract 7065: Targeting MTAP-deleted/KRAS mutant cancers using RAS inhibitors in combination with AMG 193, an MTA-cooperative PRMT5 inhibitor.

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Abstract B046: Pan-RAS Inhibition as a novel therapeutic strategy for RAS-driven rhabdomyosarcoma

Cancer Research2026-03-05

Abstract A081: Resistance Mechanisms to Monotherapy RAS(ON) Multi-Selective Inhibitor Daraxonrasib (RMC-6236) in RAS Mutant PDAC Inform Therapeutic Combination Strategies

Molecular Cancer Therapeutics2025-10-22

Abstract A118: Daraxonrasib, a RAS(ON) multi-selective inhibitor, exhibits potent antitumor activity and combinatorial benefit with standard of care chemotherapy and with anti-PD-1 in preclinical models of KRAS G12R PDAC

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A neomorphic protein interface catalyzes covalent inhibition of RAS <sup>G12D</sup> aspartic acid in tumors

Science2025-07-2414 citations

Trial in progress: RASolute 302—A phase 3, multicenter, global, open-label, randomized study of daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor, versus standard of care chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).

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Abstract CT019: Preliminary safety and antitumor activity of zoldonrasib (RMC-9805), an oral, RAS(ON) G12D-selective, tri-complex inhibitor in patients with KRAS G12D non-small cell lung cancer (NSCLC) from a phase 1 study in advanced solid tumors

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Abstract LB218: Early reduction in circulating tumor DNA (ctDNA) is associated with clinical activity of daraxonrasib (RMC-6236) in RAS mutant non-small cell lung cancer (NSCLC)

Cancer Research2025-04-25

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

Journal of Medicinal Chemistry2025-03-0832 citations

Discovery of Elironrasib (RMC-6291), a Potent and Orally Bioavailable, RAS(ON) G12C-Selective, Covalent Tricomplex Inhibitor for the Treatment of Patients with RAS G12C-Addicted Cancers

Journal of Medicinal Chemistry2025-02-2422 citations

Safety, efficacy, and on-treatment circulating tumor DNA (ctDNA) changes from a phase 1 study of RMC-6236, a RAS(ON) multi-selective, tri-complex inhibitor, in patients with RAS mutant pancreatic ductal adenocarcinoma (PDAC).

Journal of Clinical Oncology2025-01-2724 citations

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Journal of Clinical Oncology2025-01-2712 citations

Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Cancer Discovery2024-04-09213 citations

Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy.

2024-04-08215 citations

Abstract ND03: Discovery of RMC-9805, an oral, covalent tri-complex KRASG12D(ON) inhibitor

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Abstract 3874: Adaptive heterogeneity enables the survival of residual malignant PDAC cells in response to RAS-GTP inhibition

Cancer Research2024-03-22

Abstract 1927: Resistance to RAS-GTP inhibition in models of pancreatic ductal adenocarcinoma arises downstream of RAS effectors

Cancer Research2024-03-22

Abstract 1578: RAS-GTP inhibition modulates Hedgehog signaling, suppressing myCAFs and promoting iCAFs in pancreatic ductal adenocarcinoma

Cancer Research2024-03-22

Abstract B101: Tumor-selective inhibition of active RAS in pancreatic ductal adenocarcinoma

Cancer Research2024-01-16

RAS MULTI(ON) Inhibitor RMC-7977 Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 Inhibitors in AML Models

Blood2023-11-025 citations

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