2L+ NSCLC with KRAS G12C positive
Conditions
Interventions
Divarasib: Divarasib will be administered orally QD
Sotorasib: Sotorasib will be administered orally QD
Sponsors
Venice Archer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation 2. 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. Prior systemic treatment must include a platinum-based doublet chemotherapy regimen and a PD-L1/PD-1 inhibitor, either given in combination as one line of therapy or as individual lines of therapy. 3. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 4. Documentation of the presence of a KRAS G12C mutation 5. 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 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 7. Life expectancy of >= 12 weeks
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib 2. Malabsorption syndrome or other condition that would interfere with enteral absorption 3. Known concomitant second oncogenic driver 4. Mixed small-cell lung cancer or large cell neuroendocrine histology 5. Known and untreated, or active central nervous system (CNS) metastases 6. Leptomeningeal disease or carcinomatous meningitis 7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently 8. 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 9. Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor 10. More than 30 Gy of radiotherapy to the lung within 6 months of randomization 11. Uncontrolled tumor-related pain 12. Unresolved toxicities from prior anticancer therapy 13. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy 1. Progression-Free Survival (PFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| safety, efficacy, 2. Overall Survival (OS) 3. Time to Confirmed Deterioration (TTCD) on the EORTC QLQ-C30 Dyspnea Item and Physical Functioning Scale 4. TTCD on the QLQ-LC13 Cough Scale 5. Percentage of Participants with Objective Response Rate (ORR) 6. Duration of Response (DOR) 7. Percentage of Participants with Adverse Events (AEs) 8. Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI PRO-CTCAE 9. 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 10. 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) 11. 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 QLQC30 12. TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales 13. TTCD on the Chest Pain Scale of the QLQ-LC13 Scales | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Denmark, Finland, France, Germany, Greece, Hong Kong, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Republic of Korea, Singapore, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactClinical trials information
Chugai Pharmaceutical Co., Ltd.
Outcome results
None listed