Phase I/II Study of Tifcemalimab, an Anti-B and T-lymphocyte Attenuator Antibody, in Combination with Toripalimab in Previously Treated Advanced Lung Cancer

Abstract Purpose: Tifcemalimab is a recombinant humanized IgG4k monoclonal antibody targeting B and T-lymphocyte attenuator (BTLA). Co-blockade of BTLA and programmed death-1 pathways improved outcomes in non-clinical models. This phase I/II trial evaluated the safety and preliminary efficacy of tifcemalimab plus toripalimab in advanced lung cancer. Patients and Methods: Eligible patients with pathologically confirmed advanced non-small cell lung cancer (NSCLC) without sensitive epidermal growth factor receptor variation and anaplastic lymphoma kinase fusion who failed standard treatment including one programmed death-(ligand) 1 inhibitor, or refractory extensive-stage small cell lung cancer (SCLC) received tifcemalimab (200 mg) and toripalimab (240 mg) every 3 weeks intravenously until disease progression or intolerable toxicity. Simon’s two-stage optimal design was used in expansion part. The primary endpoints included safety and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Results: Totally, 24 patients with NSCLC and 43 with SCLC were enrolled (median age of all patients, 60.0 years). All patients with NSCLC and 14 (32.6%) with SCLC had received previous immunotherapy. Fifty-five (82.1%) patients experienced treatment-related adverse events (AEs), and 5 (7.5%) patients reported grade ≥3 immune-related AEs. For NSCLC, ORR was 4.3%, and disease control rate (DCR) was 47.8%; median progression-free survival (PFS) and overall survival (OS) was 1.5 and 18.9 months, respectively. For SCLC, ORR and DCR were 35.0% and 55.0%, respectively; median duration of response, PFS, and OS were 5.7, 2.8, and 12.3 months, respectively. Conclusions: Tifcemalimab plus toripalimab showed promising antitumor activities with acceptable safety, especially, in advanced refractory SCLC.