Tifcemalimab combined with toripalimab and chemotherapy as 1st line treatment for extensive-stage small cell lung cancer (ES-SCLC): A phase Ib/II, open-label study.

8089 Background: Tifcemalimab, a humanized IgG4 monoclonal antibody against B and T lymphocyte attenuator (BTLA), has shown preliminary anti-tumor activities in combination with toripalimab (anti-PD-1) as a later line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). We further conducted a multi-cohort phase Ib/II study (NCT05664971) to evaluate the safety and efficacy of tifcemalimab combined with toripalimab and chemotherapy as a 1 st line treatment for patients with advanced lung cancer. Here, we report the preliminary results from the ES-SCLC cohort. Methods: Patients without previous systemic anti-tumor therapy for ES-SCLC were eligible. Patients received tifcemalimab 200mg in combination with toripalimab 240mg and standard chemotherapy (etoposide + carboplatin/cisplatin) intravenously once every three weeks (Q3W) for 4 cycles, then followed by tifcemalimab plus toripalimab maintenance therapy until disease progression, intolerable toxicity, or completion of 2 years treatment. Primary endpoints included safety and objective response rate (ORR) by investigators per RECIST v1.1. Results: From 7/12/2023 to 12/6/2023, a total of 44 ES-SCLC patients were enrolled. As of Dec 28, 2023, the median follow-up duration was 8.3 weeks. The median age of the patients was 65.5 (range 48-73) years, and 84.1% (37/44) were males. Forty-one (93.2%) patients experienced treatment-emergent adverse events (TEAEs), and 26 (59.1%) experienced ≥ grade 3 TEAEs. The most common TEAEs included leukopenia (65.9%), neutropenia (63.6%), anemia (40.9%) and thrombocytopenia (40.9%). No treatment-related adverse events led to discontinuation of tifcemalimab and toripalimab. Four (9.1%) patients experienced immune related AE (irAEs), and 1 experienced ≥ grade 3 irAE. Among 37 evaluable patients, 32 PR and 5 SD were observed. The ORR was 86.5% (32/37) and the DCR was 100% (37/37). By the data cut-off date, 94.6% of the responses were ongoing and the median duration of response was not reached. The preliminary biomarker analysis of tumor tissue suggested 100% ORR was observed among patients with either PD-L1 or HVEM positive expression. Further biomarker analysis will be updated. Conclusions: Tifcemalimab in combination with toripalimab and chemotherapy showed a promising objective response rate with a manageable safety profile as a 1 st line treatment for patients with ES-SCLC. Continued follow-up is ongoing for additional safety and efficacy (PFS and OS) evaluation after extended exposure. Clinical trial information: NCT05664971 .