Clinical trial NCT06881784: Study of Daraxonrasib (RMC-6236) in Previously Treated Patients With RAS Mutated NSCLC (RASolve 301)
Official title: RASolve 301: Phase 3 Multicenter, Open Label, Randomized Study of RMC-6236 Versus Docetaxel in Patients With Previously Treated Locally Advanced or Metastatic RAS[MUT] NSCLC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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)
Keywords: NSCLC
Non-Small Cell Lung Cancer
Lung Cancer
RAS
KRAS
HRAS
NRAS
RAS Wild-Type
RAS Q61 Mutation
RAS G12 Mutation
RAS G13 Mutation
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2025-03-18
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival (PFS) per Investigator in the RAS G12X-C population
timeFrame: Up to approximately 4 years
measure: Overall survival (OS) in the RAS G12X-C population
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: PFS in the RAS (MUT) population per Investigator
timeFrame: Up to approximately 4 years
measure: OS in the RAS (MUT) population
timeFrame: up to approximately 4 years
measure: Objective response per Investigator in the RAS (G12X-C) and RAS (MUT) populations
timeFrame: Up to approximately 4 years
measure: PFS per BICR in the RAS (G12X-C) and RAS (MUT) populations
timeFrame: Up to approximately 4 years
measure: Objective response per BICR in the RAS (G12X-C) and RAS (MUT) populations
timeFrame: Up to approximately 4 years
measure: Duration of response (DOR) per Investigator and BICR in the RAS (G12X-C) and RAS (MUT) populations
timeFrame: Up to approximately 4 years
measure: Time to response (TTR) per Investigator and per BICR in the RAS (G12X-C) and RAS (MUT) populations
timeFrame: Up to approximately 4 years
measure: Treatment effect on quality of life (QoL) using EORTC QLQ-LC13 In the RAS (G12X-C) and RAS (MUT) populations
timeFrame: Up to approximately 4 years
measure: Treatment effect on quality of life (QoL) using EORTC QLQ-C30 In the RAS (G12X-C) and RAS (MUT) populations
timeFrame: Up to approximately 4 years
measure: Safety and tolerability in the RAS (G12X-C) and RAS (MUT) population
timeFrame: Up to approximately 4 years
measure: PK characterization of daraxonrasib In the RAS (MUT) population
timeFrame: Up to approximately 4 years
Other outcomes:
Locations:
city: Plantation
country: United States
facility: BRCR Global
state: Florida
city: Maumee
country: United States
facility: Taylor Cancer Research Center
state: Ohio
city: Nashville
country: United States
facility: SCRI Oncology Partners - Tennessee
state: Tennessee
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: San Juan
country: Puerto Rico
facility: Pan American Center for Oncology Trials
Study officials:
References: