Study of Daraxonrasib (RMC-6236) in Previously Treated Patients With RAS Mutated NSCLC (RASolve 301)

Phase 3

Recruiting

• Conditions: NSCLC (Non-small Cell Lung Cancer); Non-Small Cell Lung Cancer; NSCLC; NSCLC (Non-small Cell Lung Carcinoma); NSCLC (Advanced Non-small Cell Lung Cancer)
• Interventions: Drug: daraxonrasib; Drug: docetaxel

• Registration Number: NCT06881784
• Lead Sponsor: Revolution Medicines, Inc.

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to docetaxel.

Detailed Description

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib will improve progression free survival (PFS) or overall survival (OS) compared to docetaxel chemotherapy in patients with NSCLC who were previously treated. Patients will be randomized in a 1:1 ratio to receive daraxonrasib or docetaxel chemotherapy.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-10
• Study First Submitted QC: 2025-03-10
• Study First Posted: 2025-03-18
• Study Start: 2025-05-06
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-21
• Primary Completion: 2027-12-01
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 420

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
daraxonrasib	daraxonrasib	study drug
docetaxel	docetaxel	Patients randomized to the comparator control arm will receive docetaxel as the standard of care therapy.

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS) per Investigator in the RAS G12X-C population	Up to approximately 4 years	PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per response evaluation criteria in solid tumors (RECIST) v1.1 and as assessed by Investigator.
Overall survival (OS) in the RAS G12X-C population	Up to approximately 4 years	OS is defined as the time from randomization until death from any cause.

Secondary Outcome Measures

Name	Time	Method
PFS in the RAS (MUT) population per Investigator	Up to approximately 4 years	PFS is defined as time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per RECIST v1.1 as assessed by Investigator.
OS in the RAS (MUT) population	up to approximately 4 years	OS is defined as time from randomization until death from any cause.
Objective response per Investigator in the RAS (G12X-C) and RAS (MUT) populations	Up to approximately 4 years	Objective response of partial response (PR) or complete response (CR) per RECIST v1.1 as assessed by Investigator.
PFS per BICR in the RAS (G12X-C) and RAS (MUT) populations	Up to approximately 4 years	PFS is defined as time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per RECIST v1.1 as assessed by blinded independent central review (BICR).
Objective response per BICR in the RAS (G12X-C) and RAS (MUT) populations	Up to approximately 4 years	Objective response of PR or CR per RECIST v1.1 as assessed by BICR.
Duration of response (DOR) per Investigator and BICR in the RAS (G12X-C) and RAS (MUT) populations	Up to approximately 4 years	DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by Investigator and by BICR.
Time to response (TTR) per Investigator and per BICR in the RAS (G12X-C) and RAS (MUT) populations	Up to approximately 4 years	TTR is defined as time from randomization to first evidence of objective response (PR or CR), as assessed by Investigator and by BICR.
Treatment effect on quality of life (QoL) using EORTC QLQ-LC13 In the RAS (G12X-C) and RAS (MUT) populations	Up to approximately 4 years	Time to deterioration (TTD) in selected symptoms (dyspnea, chest pain, cough) defined as the time from randomization to the first onset of 10 points or more deterioration from baseline in the corresponding symptom scales (dyspnea, chest pain, cough) on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire LC-13 (EORTC QLQ-LC13).; Change from baseline on EORTC QLQ-LC13 in symptom scales (dyspnea, cough, chest pain).
Treatment effect on quality of life (QoL) using EORTC QLQ-C30 In the RAS (G12X-C) and RAS (MUT) populations	Up to approximately 4 years	Change from baseline in global quality of life score from European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire.; Change from baseline on EORTC QLQ-C30 functioning domains (physical role, cognitive, emotional, social).
Safety and tolerability in the RAS (G12X-C) and RAS (MUT) population	Up to approximately 4 years	Incidence of treatment emergent adverse events (TEAEs), treatment related adverse events (TRAEs), serious adverse events (SAEs), changes in vital signs and clinical laboratory tests.
PK characterization of daraxonrasib In the RAS (MUT) population	Up to approximately 4 years	Blood concentrations of daraxonrasib over time.

Trial Locations

Locations (5)

SCRI Oncology Partners - Tennessee; 🇺🇸 Nashville, Tennessee, United States

Taylor Cancer Research Center; 🇺🇸 Maumee, Ohio, United States

Utah Cancer Specialists; 🇺🇸 Salt Lake City, Utah, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Pan American Center for Oncology Trials; 🇵🇷 San Juan, Puerto Rico