Sponsor: Revolution Medicines, Inc. (industry)
Phase: 3
Start date: March 18, 2025
Planned enrollment: 420
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)
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)
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)
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)
Last updated: Sep 2026
Goal: Determine whether daraxonrasib improves progression-free survival or overall survival compared with docetaxel in previously treated RAS-mutant advanced NSCLC, while assessing safety and quality of life.
Patients: Adults with unresectable locally advanced or metastatic NSCLC harboring a KRAS, NRAS, or HRAS mutation at codon 12, 13, or 61. Patients must have measurable disease, ECOG performance status 0–1, and one or two prior lines of therapy that included platinum chemotherapy and anti-PD-1 or anti-PD-L1 treatment. Prior direct RAS-targeted therapy or docetaxel and untreated CNS metastases are exclusion criteria.
Design: Global, multicenter, open-label phase 3 trial with 1:1 randomization to daraxonrasib or docetaxel.
Treatments: Daraxonrasib (RMC-6236) is an oral RAS(ON) inhibitor that binds cyclophilin A to form a complex that engages active, GTP-bound RAS and blocks downstream signaling across multiple RAS variants. An early-phase study in previously treated RAS-mutant NSCLC reported tumor responses in more than 30% of patients; efficacy in this setting remains to be established. A separate phase 3 pancreatic cancer study reported longer survival with daraxonrasib than with chemotherapy, but those results do not establish benefit in NSCLC. Docetaxel is the standard-of-care chemotherapy comparator.
Outcomes: The primary endpoints are investigator-assessed RECIST v1.1 progression-free survival and overall survival in the RAS G12X-C population, followed for up to approximately four years. Secondary endpoints include survival in the broader RAS-mutant population; response rate, duration and time to response, and centrally reviewed progression-free survival; patient-reported symptoms and quality of life; adverse events; and daraxonrasib pharmacokinetics.
Burden on patient: Moderate expected burden: treatment and follow-up require clinic visits, imaging, laboratory monitoring, and quality-of-life questionnaires over a potentially prolonged period. Daraxonrasib can be taken orally, whereas docetaxel requires infusion visits. Blood sampling for pharmacokinetics is planned, but its frequency is not specified; no mandatory research biopsy is described.
Last updated: Sep 2026
Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.
Inclusion Criteria:
* At least 18 years old and has provided informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Histologically confirmed NSCLC, either locally advanced or metastatic, not amenable to curative surgery or radiotherapy.
* Measurable disease per RECIST v1.1.
* Adequate organ function (bone marrow, liver, kidney, coagulation).
* One to two prior lines of therapy including an anti-PD-1/anti-PD(L)-1 agent and platinum-based chemotherapy.
* Documented RAS mutation status, defined as Nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
* Able to take oral medications.
Exclusion Criteria:
* Prior therapy with direct RAS-targeted therapy or docetaxel.
* Untreated central nervous system (CNS) metastases.
* Medically significant comorbidities (significant cardiovascular disease, lung disease, or impaired GI function).
* Ongoing anticancer therapy.
* Pregnancy and/or breastfeeding.
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