This trial will evaluate the safety and dose of a new drug (Sasanlimab) in combination with different targeted therapies in patients with non-small cell lung cancerA Phase 1b/2 Open Label Umbrella Study of Sasanlimab Combined With Anti-Cancer Therapies Targeting Multiple Molecular Mechanisms in Participants With Non-Small Cell Lung Cancer (NSCLC)

Inclusion

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%