A Phase III, Randomized, Open-label Study Evaluating the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Patients With Resected Stage II-III KRAS G12C-Positive Non-small Cell Lung Cancer

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 400 participants

Study Arms

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

Interventions

• DRUG: Divarasib — Divarasib will be administered orally as per the schedule specified in the respective arm.
• DRUG: Pembrolizumab — 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).
• DRUG: Nivolumab — 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).

Primary Outcomes

• 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

• 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))

Eligibility Criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Contact Information

• Reference Study ID Number: BO45885 https://forpatients.roche.com/ — CONTACT
  Phone: 888-662-6728 (U.S. only)
  Email: global-roche-genentech-trials@gene.com

Study Officials

• Clinical Trials — STUDY_DIRECTOR
  Hoffmann-La Roche

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