Abstract CT007: A phase 2 study of tislelizumab (TIS) + investigational agents as first-line (1L) treatment in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC)

Abstract Background: Despite the use of anti-programmed cell death protein-1 (PD-1) /programmed cell death protein ligand-1 (PD-L1) monotherapy in HNSCC, not all patients (pts) experience a durable response or prolonged survival; thus, there is an unmet need for novel treatment combinations. TIS is an anti-PD-1 monoclonal antibody (mAb) that blocks the PD-1/PD-L1 immune checkpoint. Here, we present results from a phase 2, open-label, international study of TIS with or without the anti-TIM-3 mAb surzebiclimab (SUR) and/or the anti-LAG-3 mAb alcestobart (LBL-007 hereafter) as 1L treatment in pts with R/M HNSCC (NCT05909904). Methods: Eligible pts were ≥18 years with histologically/cytologically confirmed R/M HNSCC and positive PD-L1 expression CPS ≥1. Pts were randomized to receive TIS monotherapy (Arm A), TIS plus SUR (Arm B), TIS plus LBL-007 (Arm C), or TIS plus SUR and LBL-007 (Arm D). The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1. 1; secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), and safety/tolerability. Results: As of June 17, 2025, 160 pts were enrolled (40 in each arm). In the overall cohort, the median (range) age was 64. 0 (22-84) years; most pts were male (84. 4%), Asian (70. 6%), with ECOG PS of 1 (52. 5%), had the oral cavity as the primary disease location (42. 5%), and had received prior platinum-based chemotherapy (60. 0%). Median study follow-up time was 13. 1 (range: 0. 1-21. 2) months. Similar ORRs were observed across treatment arms, with confirmed ORRs (95% CI) of 27. 5% (14. 6-43. 9) in Arms A, B, and D, and 25. 0% (12. 7-41. 2) in Arm C; complete responses occurred in 3 pts in Arm C and 2 pts in Arm D. CBR (95% CI) was 32. 5% (18. 6-49. 1) in Arm A, 37. 5% (22. 7-54. 2) in Arms B and D, and 35. 0% (20. 6-51. 7) in Arm C. DCR (95% CI) was 55. 0% (38. 5-70. 7), 67. 5% (50. 9-81. 4), 62. 5 (45. 8-77. 3), and 65. 0 (48. 3-79. 4) in Arms A, B, C, and D, respectively. The treatment in each arm was well tolerated and toxicities were manageable. The most common TEAEs were anemia (23. 3%), hypothyroidism (18. 9%), and increased aspartate aminotransferase (15. 1%) in the overall cohort. Treatment-related TEAEs occurred in 67. 5%, 61. 5%, 77. 5%, and 67. 5% of pts in Arms A, B, C, and D, respectively. Fatal TEAEs occurred in 5. 7% of pts in the overall cohort, of which none were treatment related. Immune-mediated adverse events occurred in 35. 2% of pts in the overall cohort; most were grade 1 or 2 and non-serious. Infusion-related reactions occurred in 6. 9% of pts in the overall cohort, with only a single grade ≥3 event reported in Arm A. Conclusion: Overall, efficacy was comparable between treatment arms. Safety profiles were consistent with previous reports. No additional benefit accrued from adding SUR, LBL-007, or SUR and LBL-007 to TIS as 1L treatment in pts with R/M HNSCC. Citation Format: Hye Ryun Kim, Ye Guo, Cesar A. Perez, Robert Haddad, Ching-Yun Hsieh, Lei Liu, Nuttapong Ngamphaiboon, Song Qu, Saad Khan, Muh-Hwa Yang, Iris Xiang, Vivian Li, M. Brent McHenry, Jinhui Zhang, Ziwei Zhang, Kevin J. Harrington. A phase 2 study of tislelizumab (TIS) + investigational agents as first-line (1L) treatment in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT007.