A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer
- Conditions
- Non-Small Cell Lung CancerKRAS G12C Lung Cancer
- Interventions
- Registration Number
- NCT06497556
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic non-small cell lung cancer (NSCLC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 320
- Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation
- Disease progression during or after treatment with at least one prior systemic therapy but no more than three lines of prior systemic therapy in the advanced or metastatic setting
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Documentation of the presence of a KRAS G12C mutation
- Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of >= 12 weeks
- Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib
- Malabsorption syndrome or other condition that would interfere with enteral absorption
- Known concomitant second oncogenic driver
- Mixed small-cell lung cancer or large cell neuroendocrine histology
- Known and untreated, or active central nervous system (CNS) metastases
- Leptomeningeal disease or carcinomatous meningitis
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently
- Any infection that, in the opinion of the investigator, could impact patient safety, or treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 of Cycle 1
- Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
- More than 30 Gy of radiotherapy to the lung within 6 months of randomization
- Uncontrolled tumor-related pain
- Unresolved toxicities from prior anticancer therapy
- History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Divarasib Divarasib Participants will receive divarasib orally, once daily (QD). KRAS G12C inhibitor Sotorasib Participants will receive Sotorasib orally QD or adagrasib orally twice a day (BID) KRAS G12C inhibitor Adagrasib Participants will receive Sotorasib orally QD or adagrasib orally twice a day (BID)
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to approximately 4 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)
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 4 years OS is defined as the time from randomization to death from any cause
Objective Response Up to approximately 4 years Objective response is defined as complete response (CR) or partial response (PR) as determined by BICR according to RECIST v1.1
Time to Confirmed Deterioration (TTCD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Dyspnea Item and Physical Functioning Scale Baseline up to approximately 4 years TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale Baseline up to approximately 4 years Duration of Response (DOR) Up to approximately 4 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 4 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 4 years Change from Baseline in Diarrhea, Nausea, Vomiting, Anorexia, Alopecia, Dyspnea, Cough, Constipation, Myalgia, Headache, and Rash/Acne as Assessed Through use of the NCI PRO-CTCAE Baseline up to approximately 4 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 4 years Change from Baseline in Cough, Chest Pain, Dyspnea, Physical and Role Functioning, and Global Health Status score/Quality of Life Score (GHS/QoL) at Each Timepoint as Assessed Through use of the EORTC QLQ-LC13 and QLQ-C30 Baseline up to approximately 4 years TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales Up to approximately 4 years TTCD on the Chest Pain Scale of the QLQ-LC13 Scales Up to approximately 4 years
Trial Locations
- Locations (250)
Banner Health MD Anderson AZ
🇺🇸Phoenix, Arizona, United States
University of Arkansas For Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Los Angeles Cancer Network
🇺🇸Los Angeles, California, United States
UCLA Hematology / Oncology Clinic
🇺🇸Los Angeles, California, United States
Community Clinical Trials
🇺🇸Orange, California, United States
Zuckerberg San Francisco General Hospital
🇺🇸San Francisco, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
UC Health Oncology Research
🇺🇸Colorado Springs, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Bay Pines Foundation Inc
🇺🇸Bay Pines, Florida, United States
Scroll for more (240 remaining)Banner Health MD Anderson AZ🇺🇸Phoenix, Arizona, United States