NSCLC, Non-small Cell Lung Cancer, Non-Small Cell Lung Cancer NSCLC, Non-Squamous Non Small Cell Lung Cancer, Lung Cancer (NSCLC), Metastatic NSCLC - Non-Small Cell Lung Cancer, Metastatic Non-Squamous Non-Small Cell Lung Cancer
Conditions
Keywords
NSCLC, Non-Small Cell Lung Cancer, Non-Squamous Non Small Cell Lung Cancer, Metastatic Non-Squamous Non-Small Cell Lung Cancer, RAS, KRAS, NRAS, HRAS, RAS Mutation, Lung Cancer, G12D, RAS G12D
Brief summary
The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with pembrolizumab and platinum-based chemotherapy doublet compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet.
Detailed description
This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with pembrolizumab and platinum-based chemotherapy doublet will improve progression-free survival compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet when given to patients with previously untreated, 1L metastatic RAS G12D-mutated, non-squamous non-small cell lung cancer (NSCLC). Patients will be randomized to one of two arms: zoldonrasib + pembrolizumab + platinum-based chemotherapy doublet (Arm A) or placebo + pembrolizumab + platinum-based chemotherapy doublet (Arm B).
Interventions
DRUGzoldonrasib
oral tablets
DRUGPlacebo
oral tablets
DRUGpembrolizumab
IV infusion or Subcutaneous injection
IV infusion of either pemetrexed + cisplatin or pemetrexed + carboplatin
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Chemotherapy and pembrolizumab administration will be open label. This study is double-blind with respect to zoldonrasib versus placebo. Treatment assignments will remain blinded to Investigator, study center staff, patient, Sponsor and study vendors.
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. * Histologically or cytologically confirmed, previously untreated metastatic non-squamous NSCLC. * Known PD-L1 status * Documented RAS G12D mutation status. * Measurable disease per RECIST v1.1. * Adequate organ function (bone marrow, liver, kidney, coagulation, thyroid). * Able to take oral medications.
Exclusion criteria
* Prior treatment with systemic anticancer therapy in metastatic setting for NSCLC. * Prior systemic therapy with any RAS-directed therapy. * Untreated (symptomatic or asymptomatic) central nervous system metastatic disease. * Any conditions that may affect the ability to take or absorb study drug. * Major surgery on or within 28 days prior to randomization. * Patient is unable or unwilling to comply with protocol-required study visits or procedures. * Additional inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to approximately 5 years | PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is assessed per response evaluation criteria in solid tumors (RECIST) v1.1 by blinded independent central review (BICR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to approximately 5 years | OS is defined as the time from randomization until death from any cause. |
| Objective response rate (ORR) | Up to approximately 5 years | Objective response is defined as partial response (PR) or complete response (CR) as assessed per RECIST v1.1 by BICR. |
| Duration of response (DOR) | Up to approximately 5 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. Response and progression are per RECIST v1.1, as assessed by BICR. |
| Incidence of adverse events (AEs) | Up to approximately 5 years | Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 |
| Changes in vital signs | Up to approximately 5 years | Number of patients with changes in vital signs. |
| Changes in clinical laboratory test values | Up to approximately 5 years | Number of patients with changes in clinical laboratory test values. |
| Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Up to approximately 5 years | EORTC QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), 7 single item scales (pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a 2-item global health status/quality of life scale. Change from baseline in EORTC QLQ-C30 physical functioning scale and global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden. |
| Time to confirmed deterioration in physical function and global health status, as measured by EORTC QLQ-C30 | Up to approximately 5 years | Time to confirmed deterioration in physical functioning subscale and overall global health status scale, as measured by EORTC QLQ-C30. Higher scores on the Higher scores on the EORTC QLQ-C30 functional scales reflect better functioning, whereas higher scores on symptom the scales reflect higher symptom burden. Time to confirmed deterioration in EORTC QLQ-C30 physical functioning subscale and overall health status scale is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death. |
| Changes in Non-Small Cell Lung Cancer (NSCLC)-related symptoms, measured by the NSCLC-Symptom Assessment Questionnaire (NSCLC-SAQ) | Up to approximately 5 years | The NSCLC-SAQ is a participant reported outcome measure with seven items assessing key NSCLC symptoms such as: cough, pain, dyspnea, fatigue, and appetite. Change from baseline in pulmonary symptoms of cough and dyspnea will be evaluated, with higher scores indicating more severe symptoms. |
| Time to Confirmed Deterioration of NSCLC-related symptoms, as measured by NSCLC-SAQ | Up to approximately 5 years | Time to confirmed deterioration in patient-reported pulmonary symptoms of cough and dypsnea, as measured by NSCLC-SAQ. Higher scores for the pulmonary symptoms on the NSCLC-SAQ indicate more severe symptoms. Time to confirmed deterioration in NSCLC-SAQ measures is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death. |
| Concentration of zoldonrasib in Arm A | Up to Cycle 5 Day 1 (each cycle is 21 days) | Pre-dose trough and post-dose blood concentrations of zoldonrasib at selected visits. |
Countries
United States
Contacts
CONTACTRevolution Medicines Study Director
Outcome results
None listed