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 (Krascendo 1)

Roche

Status and phase: Enrolling; Phase 3

Conditions: KRAS G12C Lung Cancer; Non-Small Cell Lung Cancer

Treatments: Drug: Sotorasib; Drug: Divarasib; Drug: Adagrasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06497556

2024-510908-37-00 (Other Identifier)

BO45217

Details and patient eligibility

About

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).

Enrollment: 320 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Unequivocal histologically or cytologically confirmed diagnosis of unresectable Stage IIIc, per the American Joint Committee on Cancer staging system (AJCC) (Amin et al. 2017) not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
• 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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320 participants in 2 patient groups

Divarasib

Experimental group

Description:

Participants will receive divarasib orally, once daily (QD).

Treatment:

Drug: Divarasib

KRAS G12C inhibitor

Active Comparator group

Description:

Participants will receive Sotorasib orally QD or adagrasib orally twice a day (BID)

Treatment:

Drug: Adagrasib

Drug: Sotorasib