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

Inclusion Criteria 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%

Exclusion Criteria 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.