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
NCT Number: NCT06497556
Acronym: Krascendo 1
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Non-Small Cell Lung Cancer|KRAS G12C Lung Cancer
Interventions: DRUG: Divarasib|DRUG: Sotorasib|DRUG: Adagrasib
Sponsor: Hoffmann-La Roche
Collaborators: Chugai Pharmaceutical
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 320
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-30
Completion Date: 2028-07-31
Locations: MD Anderson Cancer Center, Houston, Texas, 77030, United States|Lyell McEwin Hospital; Clinical Trials Unit, Elizabeth Vale, South Australia, 5112, Australia|Peter Maccallum Cancer Centre, Melbourne, Victoria, 3000, Australia|Hospital Nossa Senhora da Conceicao, Porto Alegre, RS, 90040-373, Brazil|Hospital de Cancer de Barretos, Barretos, SP, 14784-400, Brazil|Pusan National University Hospital, Busan, 602-739, Korea, Republic of|Chungbuk National University Hospital, Cheongju-si, 28644, Korea, Republic of|Kyungpook National University Chilgok Hospital, Daegu, 41404, Korea, Republic of|Keimyung University Dongsan Medical Center, Daegu, 41931, Korea, Republic of|St. Vincent's Hospital, Gyeonggi-do, 16247, Korea, Republic of|Korea University Anam Hospital, Seoul, 02841, Korea, Republic of|Samsung Medical Center, Seoul, 06351, Korea, Republic of|Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, 807, Taiwan

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).

Primary Outcome Measures: Progression-Free Survival (PFS), PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first), Up to approximately 4 years
Secondary Outcome Measures: Overall Survival (OS), OS is defined as the time from randomization to death from any cause, Up to approximately 4 years|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|Percentage of Participants with Objective Response Rate (ORR), ORR is defined as the percentage of participants with a complete response (CR) or partial response (PR), as determined by the investigator according to RECIST v1.1, From randomization up to approximately 4 years|Duration of Response (DOR), DOR is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first), Up to approximately 4 years|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