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

Phase 3RecruitingNCT06881784

Revolution Medicines, Inc.420 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

420

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

daraxonrasibDRUG

oral tablets

docetaxelDRUG

intravenous (IV) infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * At least 18 years old and has provided informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Pathologically 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. * Pregnant or breastfeeding.

Locations (113)

Outcomes

Primary Outcomes

Progression free survival (PFS) per Investigator in the RAS G12X-C population (i.e RAS G12X excluding G12C)

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.

Time frame: Up to approximately 4 years

Overall survival (OS) in the RAS G12X-C population

OS is defined as the time from randomization until death from any cause.

Time frame: Up to approximately 4 years

Secondary Outcomes

PFS in the RAS (MUT) population per Investigator

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.

Time frame: Up to approximately 4 years

OS in the RAS (MUT) population

OS is defined as time from randomization until death from any cause.

Time frame: up to approximately 4 years

Objective response per Investigator in the RAS (G12X-C) and RAS (MUT) populations

Objective response of partial response (PR) or complete response (CR) per RECIST v1.1 as assessed by Investigator.

Time frame: Up to approximately 4 years

PFS per BICR in the RAS (G12X-C) and RAS (MUT) populations

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).

Time frame: Up to approximately 4 years

Central Contacts

Revolution Medicines Study Director

CONTACT

1-844-2-REVMED medinfo@revmed.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Alabama Oncology

Birmingham, Alabama, United States

RECRUITING

MemorialCare Long Beach Medical Center

Long Beach, California, United States

RECRUITING

Yale University, Smillow Cancer Center

New Haven, Connecticut, United States

RECRUITING

Florida Cancer Specialists & Research Institute - South

Fort Myers, Florida, United States

RECRUITING

BRCR Global

Plantation, Florida, United States

RECRUITING

Cancer Care Centers of Breevard

Rockledge, Florida, United States

RECRUITING

Florida Cancer Specialists & Research Institute - North

St. Petersburg, Florida, United States

RECRUITING

Cleveland Clinic Martin North

Stuart, Florida, United States

RECRUITING

Florida Cancer Specialists & Research Institute - East

West Palm Beach, Florida, United States

RECRUITING

University Cancer and Blood Center

Athens, Georgia, United States

RECRUITING

...and 103 more locations

Objective response per BICR in the RAS (G12X-C) and RAS (MUT) populations

Objective response of PR or CR per RECIST v1.1 as assessed by BICR.

Time frame: Up to approximately 4 years

Duration of response (DOR) per Investigator and BICR in the RAS (G12X-C) and RAS (MUT) populations

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 frame: Up to approximately 4 years

Time to response (TTR) per Investigator and per BICR in the RAS (G12X-C) and RAS (MUT) populations

TTR is defined as time from randomization to first evidence of objective response (PR or CR), as assessed by Investigator and by BICR.

Time frame: Up to approximately 4 years

Treatment effect on quality of life (QoL) using EORTC QLQ-LC13 In the RAS (G12X-C) and RAS (MUT) populations

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).

Time frame: Up to approximately 4 years

Treatment effect on quality of life (QoL) using EORTC QLQ-C30 In the RAS (G12X-C) and RAS (MUT) populations

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).

Time frame: Up to approximately 4 years

Safety and tolerability in the RAS (G12X-C) and RAS (MUT) population

Incidence of treatment emergent adverse events (TEAEs), treatment related adverse events (TRAEs), serious adverse events (SAEs), changes in vital signs and clinical laboratory tests.

Time frame: Up to approximately 4 years

PK characterization of daraxonrasib In the RAS (MUT) population

Blood concentrations of daraxonrasib over time.

Time frame: Up to approximately 4 years