Study of Immunotherapy (Sasanlimab) in Combination With Targeted Therapies in People With Advanced Non-small Cell Lung Cancer (NSCLC) (Landscape 1011 Study)

Open to people ages 18 years and up

Umbrella Phase 1b & 2:

- Histologically or cytologically confirmed locally advanced/metastatic (Stage IIIB-IV) NSCLC. - At least one measurable lesion per RECIST v1.1 at Screening. - ECOG Performance Status 0 or 1. - Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1. - Adequate hepatic, renal, and bone marrow function. Additional Inclusion Criteria for Sub-Study A Phase 1b &2: -BRAFV600E mutation in tumor tissue or plasma as determined by a local laboratory PCR or NGS assay and documented in a local pathology report. Additional Inclusion Criteria for Sub-Study A Phase 1b only: -Any line of therapy for locally advanced/metastatic NSCLC. Additional Inclusion Criteria for Sub-Study A Phase 2 only: -Previously untreated for locally advanced/metastatic NSCLC Additional Inclusion Criteria for Sub-Study B Phase 1b only:: -Any line of therapy for locally advanced/metastatic NSCLC. Additional Inclusion Criteria for Sub-Study B Phase 2 only: - Previously untreated for locally advanced/metastatic NSCLC (Arms B1 & B2), or - One or 2 prior lines of therapy for advanced/metastatic NSCLC (Arm B3), including immune checkpoint inhibitor treatment + chemotherapy, and have progressed during or after that therapy. - PD-L1 TPS ≥1%

Umbrella Phase 1b &2:

- Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. - Active non-infectious pneumonitis, pulmonary fibrosis, or known history of immune-mediated pneumonitis. - Active infection requiring systemic therapy. - Clinically significant cardiovascular disease. - Other malignancy within 2 years of first dose, with exceptions. - Symptomatic brain metastasis, with exceptions. Additional Exclusion Criteria for Sub-Study A Phase 1b&2: - EGFR mutation, ALK fusion oncogene, or ROS1 rearrangement. - Prior treatment with any BRAF inhibitor or MEK inhibitor. Additional Exclusion Criteria for Sub-Study A Phase 2 only: -Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents. Additional Exclusion Criteria for Sub-Study B Phase 1b&2: -Documentation of any tumor-driving molecular alteration (eg, BRAF, EGFR, ALK) Additional Exclusion Criteria for Sub-Study B Phase 2 only: - Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.(Arms B1 & B2) - Confirmed progressive disease on 1st or 2nd imaging tumor assessment after initiation of therapy for advanced/metastatic NSCLC.