Rasonque (daraxonrasib) / Revolution Medicines, Royalty, BeOne Medicines - LARVOL DELTA

Targeting KRAS-Mutant Lung Cancers. (PubMed, J Natl Compr Canc Netw) - "The first allele-specific inhibitors, sotorasib and adagrasib, validated KRASG12C as a druggable dependency, changing the treatment paradigm for previously treated KRASG12C NSCLC, although primary, acquired, and adaptive resistance remain widespread. Next-generation inhibitors such as divarasib improve potency and tolerability but continue to face resistance through secondary KRAS alterations, bypass receptor tyrosine kinase (RTK) signaling, and adaptive MAPK reactivation...Early clinical results with tricomplex RAS(ON) inhibitors (eg, daraxonrasib) and G12D-selective agents (eg, zoldonrasib) demonstrate promising activity in subsets historically lacking targeted options. In parallel, rational combination strategies aimed at enhancing overall efficacy, such as RTK, SHP2/SOS1, or PD-1/PD-L1 blockade, together with emerging modalities including RAF-MEK clamps, adoptive cell therapies, and KRAS vaccines, are broadening the therapeutic landscape. This review comprehensively..."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Pan-RAS(on) Inhibitors RMC-6236 and GFH276 With Omeprazole or Ensartinib in KRAS-mutant Lung Cancer Cells (IASLC-WCLC 2026) - "Our previous work showed that the combination of omeprazole plus tepotinib is active in KRAS-mutant G12C and non-G12C cell lines ( Rosell et al...The H23 and A549 (sotorasib-resistant) cells were sensitive to both Pan-RAS(ON) inhibitors with higher IC 50s...Finally, pretreatment with omeprazole plus Pan-RAS inhibitors suggests a potential to delay resistance. Like crizotinib, ensartinib has activity against ALK, ROS1, and MET, and additionally targets AXL; therefore, ensartinib warrants further investigation."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AXL • CTNNB1 • KRAS • ROS1 • SQSTM1 • STAT3

Daraxonrasib (Rasonque) for metastatic pancreatic cancer. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Oncology • Pancreatic Cancer • Solid Tumor

RAS-targeted therapies for pancreatic cancer. (PubMed, ESMO Gastrointest Oncol) - "Furthermore, a recent clinical trial evaluating the pan-RAS inhibitor, daraxonrasib, demonstrated a survival extension more than double that of conventional chemotherapy in previously treated metastatic PDAC. These encouraging results mark a new dawn of hope for PDAC management. In this review, we provide an updated overview of the therapeutic landscape of RAS inhibitors in PDAC and discuss the future challenges associated with these novel treatments."

IO biomarker • Journal • Review • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • KRAS

In patients with previously treated metastatic pancreatic adenocarcinoma, does daraxonrasib improve overall survival and progression-free survival compared with standard chemotherapy, while being safe? (PubMed, Rev Med Interne) - No abstract available

Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Preliminary efficacy with daraxonrasib demonstrated in RAS-mutant NSCLC. (PubMed, Nat Rev Clin Oncol) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RAS

The @FDA approved the drug daraxonrasib for advanced pancreatic cancer. It's the first to extend patients' lives. Our researchers, Drs. Mitesh Borah, an investigator on the drug trial, and Tanios Bekaii-Saab @GIcancerDoc , both leaders in novel therapeutics, share the impact.

Regulatory

Updated safety and efficacy 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) (EORTC-NCI-AACR 2024) - P1 | "RMC-6236 showed a manageable safety profile and encouraging efficacy in patients with previously treated RAS mutant PDAC. RASolute 302, a global, randomized, Phase 3 clinical trial of RMC-6236 vs standard of care chemotherapy as 2L treatment has been initiated in patients with metastatic PDAC."

Clinical • Late-breaking abstract • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Primary and final analysis from the phase 3 RASolute 302 study. (ASCO 2026) - P3 | "Daraxonrasib demonstrated unprecedented improvements in OS and PFS vs chemo in pts with 2L mPDAC with or without an identified tumor RAS mut. Daraxonrasib was generally well tolerated, with a manageable safety profile and with no new safety signals. Results support daraxonrasib as the new SOC for 2L mPDAC."

Late-breaking abstract • Metastases • P3 data • Dental Disorders • Hematological Disorders • Oncology • Pancreatic Adenocarcinoma • Stomatitis

Revolution Medicines…announced that the…FDA has granted Breakthrough Therapy Designation to RASONQUE (daraxonrasib)…for treatment-naïve metastatic pancreatic adenocarcinoma (PDAC) in combination with gemcitabine and nab-paclitaxel (GnP)… (GlobeNewswire) - "The Breakthrough Therapy Designation is based on data from patients with treatment-naïve RAS mutant metastatic PDAC who received RASONQUE in combination with GnP in the open-label, multicenter Phase 1/2 RMC-GI-102 trial."

Breakthrough therapy • Pancreatic Ductal Adenocarcinoma

A Phase 1/2 study of vopimetostat in combination with daraxonrasib or zoldonrasib in patients with MTAP deleted RAS mutated (MTAPdel/RASmut) metastatic PDAC and NSCLC (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP • RAS

Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. (PubMed, Nature) - P1 | "Here we describe RMC-7977, a reversible, tri-complex RAS inhibitor with broad-spectrum activity for the active state of both mutant and wild-type KRAS, NRAS and HRAS variants (a RAS(ON) multi-selective inhibitor). Thus, RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRAS-mutant solid tumours (ClinicalTrials.gov identifier: NCT05379985)."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HRAS • KRAS • NRAS

Safety and efficacy of zoldonrasib (RMC-9805) plus daraxonrasib (RMC-6236) in patients with 2L+ KRAS G12D metastatic pancreatic adenocarcinoma (mPDAC) (ESMO-GI 2026) - P1 | "Clinical trial identification NCT06040541. Table: 341O Conclusions Zoldonrasib + daraxonrasib showed manageable safety and compelling preliminary efficacy in 2L+ KRAS G12D mPDAC. These results support initiation of RASolute 309, a global, randomized, phase 3 study evaluating zoldonrasib + daraxonrasib vs gemcitabine + nab-paclitaxel in 1L RAS G12D mPDAC."

Clinical • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • KRAS

Exhibit Hall Presentation: RASONQUE: Breaking Barriers in Metastatic Pancreatic Adenocarcinoma by Targeting RAS Revolution Medicines (JADPRO 2026) - "Sponsored by Revolution Medicines"

Metastases • Oncology • Pancreatic Adenocarcinoma

Where Does Daraxonrasib Stand? Comparative Efficacy of Pan-RAS and KRAS G12C Inhibitors in Metastatic Pancreatic Cancer: A Systematic Review and Network Meta-Analysis (ACG 2026) - "Five studies comprising 1,194 patients were included in the network meta-analysis. The treatment network consisted of pan-RAS inhibition (daraxonrasib; n=248), KRAS G12C inhibitors (sotorasib/adagrasib; n=59), and standard chemotherapy (n=887). Daraxonrasib demonstrated superior efficacy compared with chemotherapy for overall survival (HR 0.40, 95% CI 0.30-0.53), progression-free survival (HR 0.49, 95% CI 0.38-0.64), and objective response rate (RR 2.82, 95% CI 1.95-4.08)."

Metastases • Retrospective data • Review • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Daraxonrasib: A Breakthrough in Pancreatic Ductal Adenocarcinoma. (PubMed, Cureus) - "Further, large-scale, blinded, multicenter randomized trials are required to confirm the efficacy and safety of daraxonrasib in PDAC and other solid-organ neoplasms. The orally administered daraxonrasib could be a potential game changer in the treatment of PDAC, which is otherwise considered one of the least chemotherapy-amenable human cancers."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

The ERK MAPK pathway in mesenchymal glioblastoma: tumorigenesis, microenvironmental reprogramming, and the therapeutic promise of RAS(ON) multi-selective inhibition. (PubMed, Front Mol Neurosci) - "RAS(ON) inhibition therefore holds potential to simultaneously suppress tumor proliferation and remodel the tumor microenvironment (TME) toward an anti-tumor state. In this review, we discuss the potential effect of daraxonrasib as an emerging targeted therapeutic candidate in MES-GBM, highlighting the need of further research and clinical evaluation to better determine its therapeutic efficacy dedicated GBM preclinical models."

Journal • Review • Brain Cancer • Glioblastoma • Oncology • Pancreatic Cancer • Solid Tumor • EGFR • NF1

Preliminary safety, antitumor activity, and circulating tumor DNA (ctDNA) changes with RMC-9805, an oral, RAS(ON) G12D-selective tri-complex inhibitor in patients with KRAS G12D pancreatic ductal adenocarcinoma (PDAC) from a phase 1 study in advanced solid tumors. (ASCO-GI 2025) - P1 | "Oral RMC-9805 showed encouraging initial antitumor activity with early and deep reductions in KRAS G12D ctDNA in patients with KRAS G12D PDAC. Tolerability was favorable relative to SOC chemotherapy for PDAC and manageable. This overall safety profile and antitumor activity support continued evaluation as monotherapy in patients with KRAS G12D PDAC, and in combination with chemotherapy and targeted therapies, including the RAS(ON) multi-selective inhibitor RMC-6236."

Circulating tumor DNA • Clinical • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Rasolve 301: A Phase 3 Study of Daraxonrasib (RMC-6236) vs. Docetaxel in Patients With Previously Treated RAS-Mutant NSCLC (IASLC-WCLC 2026) - P1/2, P3 | "Key secondary endpoints include PFS and OS in patients with all RAS mutations, and ORR per RECIST v1.1. The study will enroll ~420 patients globally, including from sites in the USA (including Puerto Rico)."

Clinical • IO biomarker • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • HRAS • KRAS • NRAS • RAS

RASolute 302: Lessons Learned and the Road Ahead in Pancreatic Cancer. (PubMed, Oncologist) - No abstract available

Journal • Oncology • Pancreatic Cancer • Solid Tumor

The KRAS targeting revolution in metastatic pancreatic cancer: insights from the landmark RASolute-302 trial and emerging allele-specific strategies at ASCO 2026. (PubMed, J Hematol Oncol) - "This correspondence highlights how the first-in-class pan-RAS (ON) inhibitor daraxonrasib (RMC-6236) virtually doubled median overall survival (13.2 vs. 6.6 months) and progression-free survival compared to chemotherapy in second-line mPDAC, establishing a new standard of care...These include the selective KRAS G12D inhibitor DN022150 and promising horizontal combinations pairing the G12D inhibitor HRS-4642 with either the anti-PD-L1 antibody adebrelimab or a Nectin-4-targeted antibody-drug conjugate (ADC). Furthermore, we address the KRAS G12C cohort where farnesyl transferase co-inhibition (darlifarnib plus adagrasib) successfully bypasses adaptive resistance. Ultimately, the therapeutic landscape of mPDAC is transitioning toward tailored genomic frameworks. Future success will rely on optimizing the clinical sequencing or combination of pan-RAS and allele-specific agents, guided by real-time liquid biopsies, to permanently dismantle resistance and transform mPDAC into..."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Preliminary safety, pharmacokinetics, and antitumor activity of RMC-9805, an oral, RAS(ON) G12D-selective, tri-complex inhibitor in patients with KRAS G12D pancreatic ductal adenocarcinoma (PDAC) from a phase 1 study in advanced solid tumors (EORTC-NCI-AACR 2024) - P1 | "Oral RMC-9805 showed encouraging initial antitumor activity in patients with KRAS G12D PDAC. Tolerability was favorable relative to SOC chemotherapy for PDAC and manageable across all dose levels and tumor types evaluated. This overall safety profile and antitumor activity support continued evaluation as monotherapy in patients with KRAS G12D PDAC, and in combination with chemotherapy and targeted therapies, including the RAS(ON) multi-selective inhibitor RMC-6236."

Clinical • Late-breaking abstract • Metastases • P1 data • PK/PD data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Daraxonrasib in Pancreatic Cancer: From Second-Line Breakthrough to First-Line Evidence. (PubMed, J Clin Oncol) - No abstract available

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Rasonque nabs FDA approval for previously treated metastatic pancreatic adenocarcinoma (Healio) - "'We use a lot of hyperbole in oncology,' Suneel Kamath, MD...'Terms like ‘breakthrough’ and 'game changer' are overused big time. This is not hyperbole. To have an incredibly effective drug that takes down a terrible target that is present in more than 90% of pancreatic cancers truly is a game-changing step forward.'"

Media quote • Regulatory

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). (ASCO 2025) - P1, P3 | "Eligibility includes patients ≥18 years old, ECOG performance status 0 or 1, disease progression on 1 prior line of either a 5-fluorouracil or gemcitabine-based regimen in the metastatic setting, and documented RAS mutation status (mutant or wild-type)...A 1:1 randomization of approximately 460 patients will receive daraxonrasib 300 mg daily or investigator's choice of chemotherapy (gemcitabine/nab-paclitaxel, mFOLFIRINOX, nal-IRI/5-FU/LV, or FOLFOX) until unacceptable toxicity or disease progression...Key secondary endpoints include PFS, OS, objective response and quality of life measures in the all-patient population with tumors carrying RAS mutations (G12X, G13X or Q61X) or RAS wild-type. Enrollment for the trial commenced in October 2024."

Clinical • Metastases • P3 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • HRAS • KRAS • NRAS