Print

Purpose

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).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Divarasib 		Participants will receive divarasib orally, once daily (QD).
  • Drug: Divarasib
    Divarasib will be administered orally QD
Active Comparator
KRAS G12C inhibitor 		Participants will receive sotorasib orally QD or adagrasib orally twice a day (BID)
  • Drug: Sotorasib
    Sotorasib will be administered orally QD
  • Drug: Adagrasib
    Adagrasib will be administred orally BID

Recruiting Locations

More Details

NCT ID
NCT06497556
Status
Active, not recruiting
Sponsor
Hoffmann-La Roche

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.