On April 21, 2026 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported updated clinical data from two Phase 1/2 trials of daraxonrasib, an oral RAS(ON) multi-selective inhibitor, in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC). Data from the daraxonrasib combination cohort will be presented in a late-breaking mini-symposium, and data from the monotherapy cohort will be presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 21, 2026.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Findings from both trials support daraxonrasib’s continued evaluation in the first line setting, demonstrating manageable safety and tolerability profiles along with early signs of durable antitumor activity across monotherapy and combination approaches.
"Patients with metastatic pancreatic cancer continue to face challenging outcomes," said Eileen M. O’Reilly, M.D., Winthrop Rockefeller Endowed Chair of Medical Oncology at Memorial Sloan Kettering Cancer Center, and a key investigator for the RMC-6236-001 trial. "What I find notable about these datasets is the strength of antitumor activity observed with daraxonrasib across both monotherapy and combination therapy, along with manageable safety profiles. With longer follow up, these results further support the potential of a novel RAS-targeted therapy to meaningfully improve outcomes in frontline metastatic PDAC."
"The activity observed with daraxonrasib in the first line setting, as both single-agent and combination therapy, represents a promising signal in this difficult-to-treat population," said Alan Sandler, M.D., chief development officer of Revolution Medicines. "We believe these findings support continued evaluation of daraxonrasib in the ongoing Phase 3 RASolute 303 trial in patients with previously untreated metastatic PDAC."
Daraxonrasib plus Chemotherapy as First Line Treatment for Patients with Metastatic Pancreatic Adenocarcinoma (Abstract #LB407)
RMC-GI-102 (NCT06445062) is a Phase 1/2 open-label, multicenter trial with multiple cohorts evaluating daraxonrasib-based combinations in patients with RAS mutant gastrointestinal tumors. The results to be presented at the AACR (Free AACR Whitepaper) Annual Meeting focus on patients in the first line metastatic PDAC cohort treated with daraxonrasib plus gemcitabine and nab-paclitaxel (GnP).
As of a December 1, 2025 data cutoff, 40 patients with previously untreated RAS mutant metastatic PDAC received daraxonrasib 200 mg once daily in 28-day cycles plus GnP given on a Day 1 and Day 15 schedule. In these patients, daraxonrasib plus GnP had a manageable safety profile, and the safety profile observed for the combination regimen was consistent with the known safety findings of each respective agent. The most common Grade ≥3 treatment-related adverse events (TRAEs) were anemia (33%), decreased neutrophil count (20%), and fatigue (18%). No Grade 5 TRAEs were reported. In the trial, TRAEs led to discontinuation of daraxonrasib in 5% (n=2) of patients and of GnP in 15% (n=6) of patients. The mean dose intensity was 82% for daraxonrasib and 80% for GnP.
Daraxonrasib plus GnP showed encouraging preliminary antitumor activity in patients with previously untreated RAS mutant metastatic PDAC. In patients who had at least 18 weeks of follow up prior to the data cutoff (n=40), the confirmed objective response rate (ORR) was 58% (95% confidence interval (CI): 41, 73), including one complete response. Median progression-free survival (PFS) and median overall survival (OS) were not mature at the data cutoff. The Kaplan-Meier estimate for PFS at 6 months was 84% (95% CI: 68, 93) and for OS was 90% (95% CI: 76, 96).
Daraxonrasib Monotherapy as First Line Treatment for Patients With Metastatic Pancreatic Adenocarcinoma (Abstract #LB337)
RMC-6236-001 (NCT05379985) is a Phase 1/2 open-label, multicenter trial evaluating daraxonrasib monotherapy in patients with RAS mutant solid tumors.
As of a December 1, 2025 data cutoff, patients with previously untreated RAS mutant metastatic PDAC received daraxonrasib 300 mg daily in 21-day cycles. In these patients, the safety profile observed for daraxonrasib was generally consistent with the reported safety findings for daraxonrasib monotherapy in previously treated patients. All-grade TRAEs occurred in 95% (n=38) of patients and Grade ≥3 TRAEs occurred in 38% (n=15) of patients. The most common Grade ≥3 TRAEs reported in at least 10% of patients were rash, diarrhea, and stomatitis. No Grade 4 or 5 TRAEs were reported. The mean dose intensity was 84%.
Daraxonrasib demonstrated encouraging preliminary antitumor activity in patients with previously untreated RAS mutant metastatic PDAC, with an ORR of 47% (95% CI: 31, 64), including one complete response, and a disease control rate of 92% (95% CI: 79, 98). Median PFS and median OS data were not yet mature at the data cutoff. The Kaplan-Meier estimate for PFS at 6 months was 71% (95% CI: 53, 83) and for OS was 83% (95% CI: 67, 92).
Daraxonrasib is being evaluated in four global Phase 3 clinical trials: three in PDAC (two ongoing and one completed) and one in non-small cell lung cancer (NSCLC). The company recently announced that the pivotal Phase 3 RASolute 302 clinical trial in patients with previously treated metastatic pancreatic cancer met all primary and key secondary endpoints, including PFS and OS. In the trial, daraxonrasib demonstrated an unprecedented OS benefit in all enrolled patients (the intent to treat population), including those with tumors with and without (wild type) an identified RAS mutation.
About Pancreatic Cancer and Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that annually approximately 60,000 people will be diagnosed with pancreatic cancer, and about 50,000 people will die from this aggressive disease.1
Due to the lack of early symptoms and detection methods, approximately 80% of patients are diagnosed with PDAC at an advanced or metastatic stage. It is the most commonly RAS-addicted of all major cancers, and more than 90% of patients have tumors that harbor RAS mutations.2 Metastatic PDAC remains one of the most common causes of cancer-related deaths in the U.S., with a five-year survival rate of approximately 3%.3,4
About Daraxonrasib
Daraxonrasib (RMC-6236) is an oral, direct RAS(ON) multi-selective inhibitor with the potential to help address a broad range of cancers driven by oncogenic RAS, including PDAC, NSCLC and colorectal cancer. Daraxonrasib suppresses RAS signaling by blocking the interaction of wild-type and mutant RAS(ON) with its downstream effectors.
(Press release, Revolution Medicines, APR 21, 2026, View Source [SID1234664621])