A Study to Evaluate the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Participants With Resected Stage II-III KRAS G12C-Positive Non-Small Cell Lung Cancer (NSCLC)

NCT07541170 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: BO458852025-524263-21-00
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main purpose of this study is to evaluate the efficacy of divarasib compared with investigator's choice of immunotherapy (pembrolizumab or nivolumab) or observation in participants with resected Kirsten rat sarcoma viral oncogene homolog glycine 12 to cysteine (KRAS G12C)-positive Stage II-IIIB NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) status, who have not achieved pathologic complete response (pCR) following neoadjuvant chemoimmunotherapy.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS), as Determined by the Investigator

  From randomization to disease recurrence or death from any cause (Up to approximately 5 years)

Secondary Outcomes (3)

• Overall Survival (OS)

  From date of randomization to death from any cause (up to approximately 8 years)

• DFS Rates at 2 and 3 Years, as Assessed by the Investigator

  At Year 2 and Year 3

• Number of Participants With Adverse Events (AEs)

  From randomization to 60 days after the end of study treatment (up to approximately 8 years)

Study Arms (2)

Divarasib

EXPERIMENTAL

Participants will receive divarasib, orally (PO), once daily (QD) for up to 52 cycles (1 cycle = 21 days).

Drug: Divarasib

Control: Pembrolizumab or Nivolumab or Observation

ACTIVE COMPARATOR

Participants will receive either pembrolizumab, nivolumab, or undergo observation, depending on the treatment received prior to surgery. No study treatment will be given to participants who will undergo observation.

Drug: Pembrolizumab; Drug: Nivolumab

Interventions

Divarasib DRUG

Divarasib will be administered orally as per the schedule specified in the respective arm.

Also known as: RO743584; GDC-6036

Divarasib

Pembrolizumab DRUG

Pembrolizumab will be administered as either a 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) or 395 mg subcutaneous (SC) injection Q3W, for up to 13 cycles (1 cycle = 21 days).

Also known as: Keytruda

Control: Pembrolizumab or Nivolumab or Observation

Nivolumab DRUG

Nivolumab will be administered as either a 480 mg IV infusion, every 4 weeks (Q4W) or 1200 mg SC injection Q4W, for up to 13 cycles (1 cycle = 28 days).

Also known as: Opdivo

Control: Pembrolizumab or Nivolumab or Observation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histological or cytological diagnosis of clinical Stage II-IIIB NSCLC of either non-squamous or squamous histology
• Participants must have had complete resection of NSCLC
• Prior treatment with neoadjuvant immune checkpoint inhibitor (pembrolizumab or nivolumab) in combination with histology-based platinum-based doublet chemotherapy
• Participants must be randomized within 12 weeks of their surgery date
• No evidence of disease recurrence or metastatic disease
• Documentation of the presence of a KRAS G12C mutation

You may not qualify if:

• Participants who achieve pCR following neoadjuvant treatment
• Prior treatment with a KRAS inhibitor or any other anti-cancer therapy not otherwise specified in the protocol
• Prior treatment with radiation therapy for NSCLC, with the exception of localized symptom-directed radiation prior to surgical resection
• Resolved Grade 3 or greater immune-related AE or unresolved Grade 2 or greater immune-related AE from neoadjuvant immunotherapy
• Active or history of autoimmune disease or immune deficiency
• Significant cardiovascular disease

Sponsors & Collaborators

• Hoffmann-La Roche: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: BO45885 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: April 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): January 31, 2032
• Study Completion (Estimated): March 31, 2035
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share