On April 13, Revolution Medicines announced that the Phase III RASolute 302 study of Daraxonrasib (RMC-6236) for pancreatic ductal adenocarcinoma (PDAC) achieved positive results in an interim analysis.

Daraxonrasib is an investigational oral RAS(ON) multi-selective non-covalent inhibitor independently developed by Revolution Medicines, designed to inhibit the interaction between wild-type and mutant RAS(ON) proteins and their downstream effectors, suppressing RAS signaling, thereby treating cancers driven by various common RAS mutations, including PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).

The drug has received Breakthrough Therapy Designation and Orphan Drug Designation from the FDA for the treatment of previously treated metastatic PDAC patients with G12 mutations. Additionally, Daraxonrasib has been included in the FDA Commissioner's National Priority Review Voucher Pilot Program, expected to accelerate its market approval.

Revolution Medicines has invested tremendous effort in this drug, raising $2 billion in June 2025 solely to advance its global development and commercialization progress.

Currently, Daraxonrasib has initiated 4 global registrational Phase III clinical trials, with 3 targeting PDAC (RASolute 302, RASolute 303, RASolute 304) and 1 targeting NSCLC (RASolute 301).

RASolute 302 is an ongoing global, randomized Phase III clinical trial (n=460) designed to evaluate the efficacy and safety of Daraxonrasib monotherapy (once daily, 300mg) compared to investigator's choice of standard therapy (chemotherapy) as second-line treatment for metastatic PDAC patients with confirmed or unconfirmed RAS mutations. The primary endpoints are progression-free survival (PFS) and overall survival (OS) in patients with RAS G12 mutant tumors. Secondary endpoints include PFS and OS in the overall population (intent-to-treat population), as well as objective response rate, duration of response, and patient-reported quality of life.
Results showed that compared to the chemotherapy group, Daraxonrasib group patients had significantly prolonged PFS and OS, with data demonstrating statistical significance and clinical relevance. In the overall population, the median OS for the Daraxonrasib group and chemotherapy group were 13.2 months and 6.7 months, respectively (HR=0.40, p<0.0001). Additionally, Daraxonrasib was well-tolerated, with manageable safety, and no new safety signals were identified.
Pancreatic cancer is known as the 'king of cancers', characterized by typically late diagnosis at advanced stages, resistance to standard chemotherapy, and high mortality. In the United States, approximately 60,000 people are diagnosed each year, and about 50,000 die from it. PDAC and its variants are the most common type of pancreatic cancer, accounting for about 92% of all pancreatic cancer cases. PDAC is also the tumor type with the highest incidence of RAS mutations, with over 90% of patients carrying such mutations. According to statistics, the 5-year survival rate for metastatic PDAC patients in the United States is about 3%.

These patients are in desperate need of effective therapeutic drugs, but current treatment options are limited, and drug development success rates are low. According to statistics from the Medicine Magic Cube Nextpharma database, among the 12 previously disclosed PDAC Phase III study results, only 4 studies achieved positive results.