A Phase 1 dose-escalation study to evaluate safety, pharmacokinetics, and pharmacodynamics of OSE-279, an anti-PD-1 monoclonal antibody in patients with advanced solid tumours

BACKGROUND: OSE-279 is a high affinity humanized monoclonal bivalent antibody against PD-1 with potent antitumor activity in vivo in syngeneic non-clinical models. METHODS: This phase I study assessed the safety, pharmacokinetics, pharmacodynamics and antitumor activity of OSE-279 in advanced solid tumours. RESULTS: Twenty patients received OSE-279 intravenously at 100 mg q3w (n = 2), 300 mg q3w (n = 7) and 600 mg q6w (n = 11). Median age was 61.5 (range 3-81) years, 50% were female, median number of prior metastatic lines was 2 (range 1-6). Most frequent tumour types were soft tissue sarcoma (n = 4) and anal squamous cell carcinoma (n = 3). OSE-279 monotherapy was safe. Two recommended phase 2 doses were established: 300 mg q3w and 600 mg q6w. The most common (≥10%) related TEAEs were diarrhoea, dry mouth, pruritus, chills, fatigue, headache, dysgeusia and hyperthyroidism. OSE-279 PK exhibited linear dose proportionality and mean receptor occupancy was maintained above 80% in all tested doses. There were 1 CR at 300 mg q3w, 4 PRs at 600 mg q6w and 7 SD with response duration ranging from 6.8 to 18.4 months. CONCLUSION: OSE-279 monotherapy was well tolerated with durable responses in patients with advanced solid tumours. The trial is continuing with OSE-279 combined with OSE2101, a therapeutic cancer vaccine in 1st line HLA-A2 positive PD-L1 ≥ 50% NSCLC. CLINICAL TRIAL REGISTRATION (NCT NUMBER: NCT05751798).