A Phase IIIb, Randomized, Multicenter, Open-label Study to Assess the Efficacy of Durvalumab Plus Tremelimumab Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for First-line Treatment in Metastatic Non-small Cell Lung Cancer Patients With Non-squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS (TRITON)
The purpose of the study is to assess the efficacy of durvalumab plus tremelimumab in combination with chemotherapy compared with pembrolizumab in combination with chemotherapy in metastatic NSCLC patients with non-squamous histology who have mutations and/or co-mutations in STK11, KEAP1, or KRAS.
• Histologically or cytologically documented Stage IV non-squamous NSCLC not amenable to curative surgery or radiation.
• Participants must have tumors with STK11 or KEAP1 or KRAS mutations. Co-mutations are also allowed.
• Participants must have tumors that lack activating epidermal growth factor receptor mutations and ALK fusions.
• No prior chemotherapy or any other systemic therapy for metastatic NSCLC. Participants who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred \> 6 months from end of last therapy.
• No prior exposure to immune-mediated therapy excluding therapeutic anti-cancer vaccines, within 6 months of randomization.
• WHO/ECOG performance status of 0 or 1 at enrollment and randomization.
• Minimum life expectancy ≥ 12 weeks at randomization.
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter with Computed Tomography (CT)/CT- Positron Emission Tomography or Magnetic Resonance Imaging and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines.
• Adequate organ and bone marrow function.
• Negative pregnancy test (urine or serum) for women of child-bearing potential
• Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control
• Male and Female participants and their partners must use an acceptable method of contraception.
• Body weight of \> 30 kg