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.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.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.Tifcemalimab plus toripalimab showed promising antitumor activities with acceptable safety, especially, in advanced refractory SCLC.