Umbrella Study of Sasanlimab Combined With Targeted Therapies in Participants With Non Small Cell Lung Cancer

Phase 1b/Phase 2 open-label, multi-center, parallel group umbrella study.

Sasanlimab (a PD-1 antagonist monoclonal antibody) will be combined with a different targeted therapy in each sub-study. The Phase1b part of each sub-study will evaluate the safety of the combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will evaluate the anti-tumor activity of the combination.

• Drug: Sasanlimab Prefillled syringe
  prefilled syringe
• Drug: Encorafenib
  capsules
• Drug: Binimetinib
  tablets

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

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.