Brief Summary
The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to docetaxel.
Brief Title
Study of Daraxonrasib (RMC-6236) in Previously Treated Patients With RAS Mutated NSCLC (RASolve 301)
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-844-2-REVMED
Central Contact Email
medinfo@revmed.com
Completion Date
Completion Date Type
Estimated
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)
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06881784
Org Class
Industry
Org Full Name
Revolution Medicines, Inc.
Org Study Id
RMC-6236-301
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Progression free survival (PFS) per Investigator in the RAS G12X-C population
Outcome Time Frame
Up to approximately 4 years
Outcome Description
OS is defined as the time from randomization until death from any cause.
Outcome Measure
Overall survival (OS) in the RAS G12X-C population
Outcome Time Frame
Up to approximately 4 years
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
PFS in the RAS (MUT) population per Investigator
Outcome Description
OS is defined as time from randomization until death from any cause.
Outcome Time Frame
up to approximately 4 years
Outcome Measure
OS in the RAS (MUT) population
Outcome Description
Objective response of partial response (PR) or complete response (CR) per RECIST v1.1 as assessed by Investigator.
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Objective response per Investigator in the RAS (G12X-C) and RAS (MUT) populations
Outcome Description
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).
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
PFS per BICR in the RAS (G12X-C) and RAS (MUT) populations
Outcome Description
Objective response of PR or CR per RECIST v1.1 as assessed by BICR.
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Objective response per BICR in the RAS (G12X-C) and RAS (MUT) populations
Outcome Description
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.
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Duration of response (DOR) per Investigator and BICR in the RAS (G12X-C) and RAS (MUT) populations
Outcome Description
TTR is defined as time from randomization to first evidence of objective response (PR or CR), as assessed by Investigator and by BICR.
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Time to response (TTR) per Investigator and per BICR in the RAS (G12X-C) and RAS (MUT) populations
Outcome Description
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).
Change from baseline on EORTC QLQ-LC13 in symptom scales (dyspnea, cough, chest pain).
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Treatment effect on quality of life (QoL) using EORTC QLQ-LC13 In the RAS (G12X-C) and RAS (MUT) populations
Outcome Description
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).
Change from baseline on EORTC QLQ-C30 functioning domains (physical role, cognitive, emotional, social).
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Treatment effect on quality of life (QoL) using EORTC QLQ-C30 In the RAS (G12X-C) and RAS (MUT) populations
Outcome Description
Incidence of treatment emergent adverse events (TEAEs), treatment related adverse events (TRAEs), serious adverse events (SAEs), changes in vital signs and clinical laboratory tests.
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Safety and tolerability in the RAS (G12X-C) and RAS (MUT) population
Outcome Description
Blood concentrations of daraxonrasib over time.
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
PK characterization of daraxonrasib In the RAS (MUT) population
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Prostate Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Endocrine System Cancers --- NEOPLASMS
Gastrointestinal (GI) Cancers --- NEOPLASMS
Gynecologic Cancers --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS
Prostate Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
LUNG NEOPLASMS
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
DOCETAXEL
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES