Abstract 744P
Background
Adebrelimab (SHR-1316) is a novel humanized IgG4 monoclonal antibody showing high affinity for PD-L1 in preclinical studies. This open-label, first-in-human trial aimed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary clinical efficacy in patients with advanced solid tumors who had failed standard therapy or for whom no known effective therapy was available.
Methods
The study used a standard 3+3 dose-escalation design, with additional patients (a total of ∼10-12 patients per level) enrolled for PK/PD assessment. Patients were given adebrelimab intravenously at 3, 10, 20 mg/kg, Q3W or 10 mg/kg, Q2W. The primary endpoint was safety.
Results
A total of 41 patients were enrolled and the most common tumor types were nasopharyngeal carcinoma (n=10) and non-small cell lung carcinoma (n=7). No dose limiting toxicity was observed at any level and the maximum tolerated dose was not defined. Treatment-related adverse events of grade ≥3 occurred in 9 patients (22.0%; 3 mg/kg/Q3W, n=1; 10 mg/kg/Q3W, n=4; 20 mg/kg/Q3W; n=2; 10 mg/kg/Q2W, n=2), with the most common being laboratory abnormalities (hepatic and hematological). Plasma exposure of adebrelimab increased in a dose-proportional manner over the dose range of 3-20 mg/kg/Q3W. After multiple administrations, the concentration of adebrelimab reached steady state after 3-5 treatment cycles, with no obvious accumulation observed. Receptor occupancy of PD-L1 remained above 90% after a single dose, at steady state and upon treatment discontinuation in all except for the 3 mg/kg/Q3W group. Per RECIST v1.1, the confirmed objective response rate was 24.4% (10/41; 95% CI 12.4-40.3) and the disease control rate was 58.5% (24/41; 95% CI 42.1-73.7) in the whole population. In the 10 responders, the median duration of response was 14.5 months (95% CI 3.5 months-not reached).
Conclusions
Adebrelimab showed acceptable safety profile and dose-dependent plasma exposure at 3-20 mg/kg every 3 weeks in patients with advanced solid tumors. Preliminary evidence of clinical activity was observed, which warrants further investigation.
Clinical trial identification
NCT03474289.
Editorial acknowledgement
Legal entity responsible for the study
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Funding
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Disclosure
W. Jing: Financial Interests, Personal, Full or part-time Employment: Hengrui Pharmaceuticals. Y. Shen: Financial Interests, Personal, Full or part-time Employment: Hengrui Pharmaceuticals. X. Ma: Financial Interests, Personal, Full or part-time Employment: Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.