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

Tifcemalimab is a recombinant humanized IgG4k monoclonal antibody targeting B- and T-lymphocyte attenuator. Co-blockade of B- and T-lymphocyte attenuator and programmed death-1 pathways improved outcomes in nonclinical models. This phase I/II trial evaluated the safety and preliminary efficacy of tifcemalimab plus toripalimab in advanced lung cancer. Eligible patients with pathologically confirmed advanced non-small cell lung cancer (NSCLC) without sensitive EGFR variation and anaplastic lymphoma kinase fusion who failed standard treatment including one PD-1/PD-L1 inhibitor or those with 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. The Simon two-stage optimal design was used in the expansion part. The primary endpoints included safety and objective response rate (ORR) per RECIST version 1.1. Twenty-four 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, and five (7.5%) patients reported grade ≥3 immune-related adverse events. For NSCLC, the ORR was 4.3%, and disease control rate was 47.8%. The median progression-free survival and overall survival were 1.5 and 18.9 months, respectively. For SCLC, the ORR and disease control rate were 35.0% and 55.0%, respectively. The median duration of response, progression-free survival, and overall survival were 5.7, 2.8, and 12.3 months, respectively. Tifcemalimab plus toripalimab showed promising antitumor activities with acceptable safety, especially in advanced refractory SCLC.