Phase I/II combination study of tifcemalimab with toripalimab in patients with refractory extensive stage small cell lung cancer (ES-SCLC)

8579 Background: The B- and T-lymphocyte attenuator (BTLA) is a novel inhibitory co-signaling receptor expressed on B cell, T cells and NK cells. Co-blockade of the BTLA and PD-1 pathways improved antigen specific anti-tumor T cell response. Tifcemalimab (JS004 or TAB004) is a humanized IgG4 monoclonal antibody with a hinge mutation (S228P) that binds BTLA and blocks its interaction with its ligand HVEM. In previous phase I studies, tifcemalimab has shown preliminary anti-tumor activities as monotherapy or in combination with toripalimab (anti-PD-1) with a manageable safety profile in patients with advanced malignancies. Methods: Eligible ES-SCLC patients refractory to prior therapies were enrolled in this I/II study (NCT05000684). Patients received 200mg tifcemalimab and 240mg toripalimab intravenously once every three weeks until disease progression, intolerable toxicity or 2 years of treatment. Study objectives included safety, anti-tumor activity and correlative biomarkers. Results: As of Jan 31, 2023, a total of 43 ES-SCLC patients refractory to prior therapy were enrolled. The median age was 60.0 (range 38-75) years. The median prior line of therapy was 1 and 14 (32.6%) patients received prior anti-PD-1/L1 treatment. By the cut-off date, the median follow-up duration was 12.1 weeks. Thirty-two (74.4%) patients experienced treatment-emergent adverse events (TEAEs); 12 (27.9%) patients experienced grade ≥ 3 TEAEs. The most common TEAEs were hyponatraemia (16.3%), alanine aminotransferase increased (14%), aspartate aminotransferase increased (14%), and blood creatine phosphokinase increased (14%). Three (7.0%) patients experienced treatment-related adverse events (TRAEs) led to interruption of study drugs and no TRAEs led to discontinuation of study drugs were reported. Fifteen (34.9%) patients experienced immune related AE (irAEs), and 2 (4.7%) patients experienced grade ≥ 3 irAEs. Among 38 efficacy evaluable patients, the ORR was 26.3% and the DCR was 57.9%. The ORR was 8.3% in immunotherapy treated patients and 40.0% in immunotherapy naïve patients. By the cut-off date, 70.0% of the responses were ongoing and the median duration of response was not reached. Tumor expression of HVEM and PD-L1 was evaluated to explore the correlation with clinical response. Conclusions: Tifcemalimab in combination with toripalimab were well tolerated in patients with refractory ES- SCLC. Further clinical evaluation of this combination treatment in SCLC is warranted. Clinical trial information: NCT05000684 .