Anti-programmed death-1 (PD-1)-based immunotherapy improved clinical response and prolonged survival in patients with solid tumors in previous studies. HLX10 is a fully humanized IgG4 monoclonal antibody binding to human PD-1, which has been shown to block ligand binding and potentiate T-cell activation and cytokine release in vitro. HLX10 has exhibited anti-tumor activity in xenograft animal models. HLX10 has shown dose-proportional ph🔜armacokinetic (PK) properties and was well-tolerated in doses up to 50 mg/kg in cynomolgus monkeys. Here we report da🤡ta from a Phase 1 study of HLX10 in patients with advanced or metastatic solid tumors (HLX10-001, NCT0346875) and introduce an ongoing clinical trial that tests its application as a combination therapy with a bevacizumab biosimilar in advanced cancer (HLX10HLX04-001, NCT03757936)
Study Design
We conducted a multicenter,open-label, dose-escalation study of HLX10 in patients with advanced or metastatic s✱olid tumors refractory to standard therapy. The Bayesian optimal interval (BOIN) design was used for establishing the maximum tolerated dose(MTD). Patients received intravenous infusion of 0.3, 1, 3, or 10mg/kg of HLX10 every two weeks, until disease progression, study withdrawal, pregnancy, death, or unacceptable toxicity up to one yea🎀r. Dose-limiting toxicity (DLT) rate was assessed over the first 4 weeks of treatment. Assessment of treatment response was performed every 8 weeks in the first 24 weeks and every 12 weeks there after. Clinical efficacy was evaluated by referencing to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and a modified RECIST1.1 for immune-based therapeutics (iRECIST). Pharmacokinetics (PK), pharmacodynamics (PD) and safety data were collected throughout the study.
Results
The clinical trial was conducted in Taiܫwan. As of 28th Oct 2019, a total o🃏f 19 patients were enrolled in the study. 57.9% of patients were male with the median age of 60 years.
Efficacy
Among 19 evaluable patients,one patient in 3mg/kg cohort♔ achieved a partial response (PR) and ꧒eight patients across all cohorts reached stable disease (SD).
Pharmacokinetics
PK profiles of HLX10 demonstrated a dose-propor༒tional manner with each escalated dose of HLX10.
Safety
HLX10 was generally♍ well-tolerated and most adverse events (AEs) were grade 1-2. One patient in the cohort of 3mg/kg experienced DLT. Grade 3 or worse AEs were reported in 7 (36.8%) patients, with non-cardiac chest pain being the most common (2 [1𝔍0.5%]).
Conclusion
•HLX10 was well-tolerated in patients with recurrent or metastatic solid tumors and elicited durable anti-tumo🍸r responses in patients with multiple solid ꦺtumors.
•The clinical benefits and safety of HLX10 warranted further investigation in an ongoing HLX10HLX04-001 trial evaluating the combination therapy of HLX10 and HLX04 (🦄a bevacizumab biosimilar) in patients with advanced solid tumors refractory to standard therapy.