Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)

This is a multicenter, randomized, open-label, international, Phase 3 trial to evaluate the efficacy and safety of acasunlimab in combination with pembrolizumab versus docetaxel (standard of care) in participants with locally advanced (unresectable stage IIIB/C) or programmed death ligand 1 (PD-L1)-positive metastatic non-small cell lung cancer (NSCLC) who have been treated with programmed cell death protein 1 (PD-1)/PD-L1 inhibitor and platinum-containing chemotherapy, administered either in combination or sequentially in the locally advanced (unresectable stage IIIB/C) or metastatic setting.

Key Inclusion Criteria: * Participant has histologically or cytologically confirmed locally advanced (unresectable stage IIIB/C) or metastatic NSCLC (stage IV) with known subtype. * Participant has progressed radiographically on or after receiving: * One prior line of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy concomitantly) in the locally advanced (unresectable stage IIIB/C) or metastatic disease setting; OR * No more than 2 prior lines of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy sequentially, irrespective of the order) in the locally advanced (unresectable stage IIIB/C) or metastatic disease setting. * Participant must have positive tumor PD-L1 expression (tumor cells ≥1%) determined prospectively on a tumor sample from the locally advanced (unresectable stage IIIB/C) or metastatic setting at a sponsor-designated central laboratory. * Participant has measurable disease according to RECIST v1.1 as assessed by the investigator at baseline. * Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 7 days of Cycle 1 Day 1. * Participant has a life expectancy of ≥3 months. * Participant must have adequate organ and bone marrow function, per laboratory test results within 7 days of trial treatment. Key Exclusion Criteria: * Documentation of known targetable epidermal growth factor receptor (EGFR) sensitizing mutations, anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), ROS proto-oncogene 1; receptor tyrosine kinase (ROS1) rearrangement, Kirsten rat sarcoma virus (KRAS), B-Raf proto-oncogene (BRAF) mutations, and MET proto-oncogene; receptor tyrosine kinase (MET) exon 14 skipping mutations/MET amplification. NOTE: MET amplification testing is optional based on local availability of the test. * Participants with known KRAS/BRAF mutations are eligible for the trial if they do not have access to targeted therapies. * Participants with newly identified, untreated or unstable or symptomatic central nervous system (CNS) metastases or history of carcinomatous meningitis. * Prior treatment with docetaxel for NSCLC. * Prior treatment with a 4-1BB (CD137) targeted agent, any type of antitumor vaccine, autologous cell immunotherapy, or any unapproved immunotherapy. * Treatment with an anticancer agent within 28 days prior to the first dose of trial treatment. Note: Other protocol-defined inclusion and exclusion criteria may apply.