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

ID#: NCT06497556

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: September 23, 2024

End Date: September 30, 2029

Contact Information:
Reference Study ID Number
888-662-6728 (U.S. and Canada)
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).
Eligibility:

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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