Non-Small Cell Lung Cancer, NSCLC, NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC (Non-small Cell Lung Cancer), NSCLC (Non-small Cell Lung Carcinoma)
Conditions
Keywords
NSCLC, Non-Small Cell Lung Cancer, Lung Cancer, RAS, KRAS, HRAS, NRAS, RAS Q61 Mutation, RAS G12 Mutation, RAS G13 Mutation
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.
Interventions
DRUGdaraxonrasib
oral tablets
DRUGdocetaxel
intravenous (IV) infusion
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The central reader of the tumor scans will be masked to the patients' treatment arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) per Blinded Independent Central Review (BICR) in the RAS G12X-C population (i.e RAS G12X excluding G12C) | 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 BICR. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| PFS in the RAS (MUT) population per BICR | 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 BICR. |
| 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 BICR 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 BICR. |
| PFS per Investigator 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 Investigator. |
| Objective response per Investigator 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 Investigator. |
| Duration of response (DOR) per Investigator and per 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 | Predose and post-dose blood concentrations of daraxonrasib over time. |
Countries
Australia, Belgium, France, Germany, Hong Kong, Ireland, Italy, Japan, Netherlands, New Zealand, Poland, Puerto Rico, Singapore, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
CONTACTRevolution Medicines Study Director
Outcome results
None listed