Evaluation of the safety and efficacy of ivonescimab in combination with ligufalimab as first-line (1L) treatment for PD-L1 positive recurrent/metastasis head and neck squamous cell carcinoma (R/M HNSCC)

BackgroundDespite PD-1 inhibitors having been approved as 1L treatment for R/M HNSCC with a median overall survival of about 12 months, new treatment strategies are needed to further improve the survival benefit. CD-47 is a macrophage immune checkpoint overexpressed in HNSCC and may correlate with immunosuppressive status, including elevated expression of PD-(L)1. Ligufalimab is a novel humanized IgG4 anti-CD-47 monoclonal antibody, and ivonescimab is an anti-PD-1/VEGF bispecific antibody. The antitumor effects of ivonescimab plus ligufalimab were encouraging in various xenograft models (reference). Therefore, we aimed to investigate the efficacy and safety of ivonescimab plus ligufalimab in patients (pts) with PD-L1 positive R/M HNSCC.MethodsIn this open-label, multi-center phase II study, eligible R/M HNSCC pts with PD-L1 positive disease (CPS≥1) were enrolled, including oropharynx, hypopharynx, larynx or oral cavity cancer. Patients were treated with ivonescimab (10 mg/kg Q3W) monotherapy or in combination with ligufalimab (45 mg/kg Q3W). The primary endpoint was objective response rate (ORR) per RECIST v1.1 assessed by investigator.ResultsAs of Mar 19, 2024, 30 pts were enrolled with the median age of 60 (range: 34-75) years, 100% had ECOG 1 and 56.7% had CPS≥20. Of 10 pts in the ivonescimab monotherapy group, an ORR of 30.0% and a DCR of 80.0% were observed, median DoR was not reached and median PFS was 5.0 months. Of 20 pts in the ivonescimab plus ligufalimab group, ORR and DCR were 60.0% and 90.0%, median DoR was not reached and median PFS was 7.1 months, 6-month PFS rate was 71.8%. In the ivonescimab plus ligufalimab group in 11 pts with CPS≥20, ORR and DCR were 72.7% and 81.8%, and in 9 pts with 1≤CPS<20 the ORR and DCR were 44.4% and 100.0%. Treatment-related adverse events (TRAEs) in all pts occurred in 20 (66.6%) pts, 1 (3.3%) pt experienced grade 3-4 TRAEs, and no TRAEs led to treatment discontinuation or death. The most common TRAEs were proteinuria (n=5) and hypothyroidism (n=4).ConclusionsIvonescimab with or without ligufalimab showed promising anti-tumor activity in pts with PD-L1 positive R/M HNSCC with a favorable safety profile.Clinical trial identificationNCT05229497.Legal entity responsible for the studyAkeso Biopharma, Inc.FundingAkeso Biopharma, Inc.DisclosureW. Li, Z.M. Wang, B. Li, Y. Xia: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc. All other authors have declared no conflicts of interest.