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.