Non-Small Cell Lung Cancer, KRAS G12C Lung Cancer
Conditions
Keywords
Advanced Non-Small Cell Lung Cancer, KRAS G12 Lung Cancer, Advanced Lung Cancer, Metastatic lung cancer, Divarasib, KRAS G12C Inhibitor, KRAS G12C Positive, KRAS Mutation, KRAS G12C Mutation, Lung Cancer Mutation
Brief summary
The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).
Interventions
DRUGDivarasib
Divarasib will be administered orally QD
DRUGPembrolizumab
Pembrolizumab will be administered via IV infusion Q3W
DRUGPemetrexed
Pemetrexed will be administered via IV infusion Q3W
DRUGCarboplatin
Carboplatin will be administered via IV infusion Q3W
DRUGCisplatin
Cisplatin will be administered via IV infusion Q3W
Sponsors
Hoffmann-La Roche
Chugai Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histologically or cytologically confirmed diagnosis of advanced or metastatic non squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy * Measurable disease, as defined by RECIST v1.1 * No prior systemic treatment for advanced or metastatic NSCLC * Documentation of the presence of a KRAS G12C mutation * Documentation of known PD-L1 expression status in tumor tissue * Availability of a representative tumor specimen * Adequate end-organ function * Eligible to receive a platinum-based chemotherapy regimen
Exclusion criteria
Related to NSCLC: * Known concomitant second oncogenic driver with available targeted treatment * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>=2 weeks prior to randomization * History of leptomeningeal disease * Uncontrolled tumor-related pain * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 5 years | PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first) |
| Overall Survival (OS) | Up to approximately 5 years | OS is defined as the time from randomization to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response | Up to approximately 5 years | Objective response is defined as complete response (CR) or partial response (PR) on two consecutive occasions \>=4 weeks apart, as determined by BICR according to RECIST v1.1 |
| Change from Baseline on the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (EORTC QLQ-LC13) Cough Scale | Baseline up to Cycle 5 Day 1 (each cycle is 21 days) | — |
| Change from Baseline on the EORTC Quality of Life Questionnaire (QLQ-C30) Dyspnea Item and Physical Functioning Scale | Baseline up to Cycle 5 Day 1 (each cycle is 21 days) | — |
| Duration of Response (DOR) | Up to approximately 5 years | DOR is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by BICR according to RECIST v1.1, or death from any cause (whichever occurs first) |
| Percentage of Participants with Adverse Events (AEs) | Up to approximately 5 years | — |
| Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to approximately 5 years | — |
| Change from Baseline in the Severity of Selected Symptomatic Treatment Toxicities as Assessed Through use of the NCI PRO-CTCAE | Up to approximately 5 years | — |
| Frequency of Participants' Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the single-item EORTC Item List (IL46) | Up to approximately 5 years | — |
| Change from Baseline on the EORTC QLQ-C30 and QLQ-LC13 Functional and Global Health Status Score/Quality of Life Score (GHS/QoL) | Up to approximately 5 years | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Portugal, Singapore, South Africa, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
CONTACTReference Study ID Number: CO45042 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed