01—Abstract
Summary
Summary of the 8-K filed September 10, 2025. Cited figures are marked; the original filing is the authoritative source.
On September 10, 2025, Revolution Medicines, Inc. disclosed under Item 8.01 (Other Events) updated pipeline data for daraxonrasib, its RAS(ON) multi-selective inhibitor, across three settings in RAS-mutant metastatic pancreatic ductal adenocarcinoma (PDAC).
In previously treated (second-line or later) patients receiving 300 mg daily from the Phase 1 RMC-6236-001 study, with a June 30, 2025 data cutoff, 83 patients were evaluated for safety; 96%a experienced any-grade treatment-related adverse events (TRAEs), 34% had Grade 3 or higher, and none discontinued treatment due to TRAEs. Among 26 patients with RAS G12X tumors, the objective response rate was 35% and disease control rate 92%; among 38 patients with RAS G12X, G13X, or Q61X tumors, these were 29% and 95%. Median progression-free survival was 8.5 months (G12X) and 8.1 months (RAS mutant), and median overall survival was 13.1 months and 15.6 months, respectively.
In first-line (treatment-naive) patients receiving daraxonrasib 300 mg daily, with a July 28, 2025 data cutoff, 40 patients were evaluated for safety, with 95%b experiencing any-grade TRAEs and 35% Grade 3 or higher; 4 patients (10%) discontinued due to TRAEs. Among 38 efficacy-evaluable patients, the objective response rate was 47% (18 of 38) and disease control rate was 89% (34 of 38). Separately, in the Phase 1 RMC-GI-102 study, daraxonrasib at 200 mg daily combined with gemcitabine and nab-paclitaxel (GnP) in first-line patients showed an objective response rate of 55% (17 of 31) and disease control rate of 90% (28 of 31) among 31 efficacy-evaluable patients; 98% experienced any-grade TRAEs and 58% Grade 3 or higher, with 2 patients (5%) on daraxonrasib and 3 (8%) on GnP discontinuing due to TRAEs.
The company stated these preliminary observations support continued development of daraxonrasib in RAS-mutant PDAC and its plans to initiate RASolute 303, a global, randomized Phase 3 trial in first-line metastatic PDAC comparing daraxonrasib monotherapy, daraxonrasib plus GnP, and a GnP control arm. The filing includes standard forward-looking statement cautions noting that prior trial results may not predict future outcomes.
02—Key points
Key Highlights
- Second-line PDAC (300 mg daily, 83 patients, June 30, 2025 cutoff): objective response rate 35% (9 of 26) in RAS G12X tumors and 29% (11 of 38) in RAS G12X, G13X, or Q61X tumors; disease control rate 92% and 95%, respectively.
- Second-line median overall survival of 13.1 months (RAS G12X) and 15.6 months (RAS mutant); median progression-free survival of 8.5 and 8.1 months.
- Second-line safety: 96% any-grade TRAEs, 34% Grade 3 or higher, rash in 90% (7% Grade 3+); no patients discontinued due to TRAEs, though 48% had dose modifications.
- First-line monotherapy (300 mg daily, 40 patients, July 28, 2025 cutoff): objective response rate 47% (18 of 38) and disease control rate 89% (34 of 38) among efficacy-evaluable patients.
- First-line combination with GnP (RMC-GI-102, 200 mg daily, 40 patients): objective response rate 55% (17 of 31) and disease control rate 90% (28 of 31); 98% any-grade TRAEs and 58% Grade 3 or higher.
- Company plans to initiate RASolute 303, a global randomized Phase 3 trial in first-line metastatic PDAC with three arms: daraxonrasib monotherapy, daraxonrasib plus GnP, and a GnP control.
03—Questions
Frequently Asked Questions
What were the main safety findings for daraxonrasib in these studies?
The most common treatment-related adverse events were rash and gastrointestinal toxicities such as stomatitis/mucositis, diarrhea, nausea, and vomiting. In second-line patients, 96% had any-grade TRAEs and 34% had Grade 3 or higher, with no discontinuations due to TRAEs. In first-line monotherapy, 95% had any-grade TRAEs and 35% Grade 3 or higher, with 10% discontinuing. The combination with GnP showed 98% any-grade and 58% Grade 3 or higher TRAEs, with 5% of daraxonrasib patients and 8% of GnP patients discontinuing.
How did patients respond to daraxonrasib in previously treated pancreatic cancer?
As of the June 30, 2025 data cutoff, the objective response rate was 35% (9 of 26) for RAS G12X tumors and 29% (11 of 38) for RAS G12X, G13X, or Q61X tumors, with disease control rates of 92% and 95%. Median overall survival was 13.1 months and 15.6 months, respectively, and median progression-free survival was 8.5 and 8.1 months. The filing describes these as preliminary observations.
What is the company's next development step for first-line pancreatic cancer?
Revolution Medicines stated that the preliminary first-line data support its plans to initiate RASolute 303, a global, randomized Phase 3 trial in patients with first-line metastatic PDAC. The three-arm trial would evaluate daraxonrasib monotherapy and daraxonrasib plus GnP, compared with a GnP control arm.
Are these results final or confirmatory?
No. The company describes the data as preliminary or initial, with different data cutoff dates (June 30, 2025 for second-line and July 28, 2025 for first-line), median follow-up periods of roughly 7 to 17 months depending on the cohort, and small patient numbers in several efficacy analyses. The filing notes that results of prior trials may not predict future outcomes.
04—Continue