REDWOOD CITY, Calif., July 2, 2026
Revolution Medicines announced encouraging Phase 1/2 clinical results for its investigational RAS(ON) G12D-selective inhibitor zoldonrasib in two combination regimens for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) harboring RAS G12D mutations. The findings, presented at the 2026 ESMO Gastrointestinal Cancers Congress, demonstrated strong antitumor activity, durable disease control, and manageable safety profiles in both previously untreated and previously treated patients. The results further strengthen the company’s late-stage development strategy, with Phase 3 RASolute 305 already underway and RASolute 309 planned for initiation.
Zoldonrasib Plus Chemotherapy Delivers High Response Rates in First-Line PDAC
AThe ongoing RMC-GI-102 Phase 1/2 study evaluated zoldonrasib in combination with investigator-selected standard chemotherapy, including modified FOLFIRINOX (mFFX) or gemcitabine plus nab-paclitaxel (GnP), in patients with previously untreated metastatic RAS G12D PDAC. As of the February 8, 2026 data cutoff, 81 patients had been enrolled across both treatment arms. The combination demonstrated a manageable safety profile, with adverse events largely consistent with known chemotherapy toxicities and no Grade 5 treatment-related adverse events reported. Importantly, the regimen achieved an objective response rate (ORR) of 82% and a disease control rate (DCR) of 96% in the mFFX cohort, while patients receiving GnP achieved an ORR of 61% and DCR of 90%. These encouraging efficacy outcomes support the ongoing global Phase 3 RASolute 305 trial, which is evaluating zoldonrasib plus chemotherapy versus chemotherapy alone as a potential first-line treatment for metastatic RAS G12D pancreatic cancer.
Dual RAS Inhibition Shows Durable Activity in Previously Treated Patients
A second Phase 1 study, RMC-9805-001, evaluated zoldonrasib combined with daraxonrasib, Revolution Medicines’ investigational RAS(ON) multi-selective inhibitor, in patients with previously treated metastatic RAS G12D PDAC. Among 60 patients, the dual-targeted combination demonstrated a manageable tolerability profile, with only 35% experiencing Grade 3 or higher treatment-related adverse events and very few treatment discontinuations. Clinical activity was particularly notable in heavily pretreated patients. In the second-line cohort, the combination achieved a 50% objective response rate, 97% disease control rate, median progression-free survival (PFS) of 9.6 months, and a 6-month overall survival rate of 89%. Patients receiving treatment in the third-line or later setting achieved an ORR of 47%, 90% disease control, median PFS of 7.6 months, and median overall survival of 10.5 months. These results support the company’s planned Phase 3 RASolute 309 trial, which will compare zoldonrasib plus daraxonrasib against standard chemotherapy in first-line metastatic RAS G12D PDAC.
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Phase 3 Development Expands for Targeted RAS G12D Therapy
According to Dr. Alan Sandler, Chief Development Officer at Revolution Medicines, the latest findings build on the clinical validation of RAS(ON) inhibition and establish two distinct therapeutic strategies for RAS G12D pancreatic cancer. One strategy combines zoldonrasib with standard chemotherapy for newly diagnosed metastatic patients, while the second utilizes dual RAS inhibition with zoldonrasib plus daraxonrasib. Pancreatic ductal adenocarcinoma remains one of the deadliest cancers, with over 90% of tumors driven by RAS mutations and approximately 40% harboring the RAS G12D subtype, making it one of the largest populations lacking an approved targeted therapy. Revolution Medicines is advancing a comprehensive late-stage clinical development program to address this significant unmet medical need, aiming to deliver more effective precision therapies for patients with RAS-driven cancers.
Source: Revolution Medicines press release
