Revolution Medicines, Inc., a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, announced results from two Phase 1/2 clinical trials evaluating zoldonrasib, its oral RAS(ON) G12D-selective covalent inhibitor, in combination regimens for patients with RAS G12D metastatic pancreatic ductal adenocarcinoma (PDAC).
The results, which will be presented in a proffered paper session at the 2026 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress, include zoldonrasib in combination with standard of care chemotherapy in previously untreated patients and zoldonrasib in combination with daraxonrasib, the company’s oral RAS(ON) multi-selective inhibitor, in previously treated patients.
“The Phase 3 RASolute 302 results provided clinical validation of RAS(ON) inhibition with daraxonrasib in second line metastatic pancreatic cancer and established a strong foundation for evaluating this therapeutic approach across additional RAS genotypes, treatment settings and combination strategies," said Alan Sandler, M.D., chief development officer of Revolution Medicines.
"The results presented at ESMO GI demonstrate compelling proof-of-concept for two zoldonrasib-based regimens in RAS G12D disease: combination with standard of care chemotherapy in previously untreated patients and a RAS(ON) inhibitor doublet with daraxonrasib in previously treated patients. Together, these findings are the foundation of two distinct Phase 3 strategies we are pursuing in previously untreated metastatic RAS G12D pancreatic cancer: the ongoing RASolute 305 trial evaluating zoldonrasib plus standard of care chemotherapy, and the planned RASolute 309 trial evaluating the combination of zoldonrasib plus daraxonrasib”.
RMC-GI-102 is an ongoing Phase 1/2 trial evaluating zoldonrasib 1200 mg once daily in combination with investigator's choice of standard of care chemotherapy in patients with previously untreated metastatic RAS G12D PDAC. Investigator's choice of chemotherapy includes modified FOLFIRINOX (mFFX) or gemcitabine plus nab-paclitaxel (GnP). As of the February 8, 2026 data cutoff, the trial enrolled 41 patients in the zoldonrasib plus mFFX arm and 40 patients in the zoldonrasib plus GnP arm.
Zoldonrasib demonstrated a manageable safety and tolerability profile in combination with standard chemotherapy. The safety profile of zoldonrasib in combination with chemotherapy was broadly consistent with the established profiles of each respective chemotherapy regimen.
In the trial, zoldonrasib with chemotherapy showed compelling antitumor activity.
RMC-9805-001 is a Phase 1 trial evaluating zoldonrasib 1200 mg once daily plus daraxonrasib 300 mg once daily in advanced solid tumors with RAS G12D mutations. As of the February 9, 2026 data cutoff, 60 patients with RAS G12D metastatic PDAC who had previously received one or more prior lines of therapy were treated with the combination.
Zoldonrasib plus daraxonrasib demonstrated a manageable safety and tolerability profile that was broadly consistent with the established profile of daraxonrasib monotherapy.
The safety and clinical activity data support the planned pivotal global, Phase 3 RASolute 309 clinical trial of zoldonrasib plus daraxonrasib versus GnP in patients with previously untreated RAS G12D metastatic PDAC. |