RASolute 303: A Phase 3 Global, Multicenter, Open-label, Randomized, 3-Arm Study of Daraxonrasib Monotherapy or Daraxonrasib Plus Gemcitabine and Nab-paclitaxel Versus Gemcitabine and Nab-paclitaxel as a First-Line Treatment for Patients With Metastatic Pancreatic Adenocarcinoma

The purpose of this study is to evaluate the safety and efficacy of an investigational RAS(ON) inhibitor administered as monotherapy or in combination with chemotherapy, compared with standard of care (SOC) chemotherapy alone.

More details:

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib monotherapy or daraxonrasib plus gemcitabine and nab-paclitaxel will improve progression-free survival and/or overall survival compared with standard gemcitabine and nab-paclitaxel when given as first-line treatment in patients with metastatic pancreatic adenocarcinoma. Patients will be randomized to one of three arms: daraxonrasib (Arm A), daraxonrasib + gemcitabine and nab-paclitaxel (Arm B), or gemcitabine and nab-paclitaxel (Arm C).

Overview

Daraxonrasib (RMC-6236; brand name Rasonque) is an oral cancer drug developed by Revolution Medicines. Although research into additional uses continues, it is no longer investigational for all uses: the US FDA approved it on August 26, 2026, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. (fda.gov)

Mechanism of action

Daraxonrasib inhibits the active, GTP-bound form of RAS. It binds the cellular protein cyclophilin A; the resulting complex engages RAS and blocks downstream signaling. Its activity spans multiple mutant and wild-type RAS variants rather than a single mutation. (sciencedirect.com)

Efficacy

In the randomized phase 3 RASolute 302 trial, 500 patients with previously treated metastatic pancreatic cancer received daraxonrasib or the investigator’s choice of chemotherapy. Median overall survival was 13.2 versus 6.7 months in the full study population, and median progression-free survival was 7.2 versus 3.6 months, respectively. Objective response rates were 31.6% versus 11.2%. These results concern previously treated metastatic disease; they do not establish benefit in other settings. (pubmed.ncbi.nlm.nih.gov)

A separate early-phase study in previously treated RAS-mutant non-small-cell lung cancer reported tumor responses in more than 30% of patients. That use remains under study. (pubmed.ncbi.nlm.nih.gov)

Safety

In RASolute 302, adverse events of grade 3 or higher occurred in 61.8% of daraxonrasib recipients and 69.6% of chemotherapy recipients; treatment-related adverse events led to discontinuation in 1.2% and 11.2%, respectively. Earlier pancreatic-cancer trial results identified rash, diarrhea, nausea, mouth inflammation, vomiting and fatigue among treatment-related adverse events reported in at least 10% of patients. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Phase 3 pancreatic-cancer trial, New England Journal of Medicine
• FDA approval announcement
• Daraxonrasib discovery and mechanism, Journal of Medicinal Chemistry

Last updated: Sep 2026

Inclusion Criteria:

* At least 18 years old and has provided informed consent.

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

* Histologically or cytologically confirmed pancreatic adenocarcinoma.

* Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.

* Documented RAS mutation status, either mutant or wild-type.

* Measurable disease per RECIST v1.1.

* Adequate organ function (bone marrow, liver, kidney, coagulation).

* Able to take oral medications.

Exclusion Criteria:

* Prior treatment with systemic anticancer therapy in metastatic setting or prior RAS-targeted therapy in any treatment setting.

* Active or known history of untreated central nervous system metastatic disease.

* Any conditions that may affect the ability to take or absorb study drug.

* Major surgery within 28 days prior to randomization.

* Patient is unable or unwilling to comply with protocol-required study visits or procedures.