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 pharmacokinetic (PK) properties and was well-tolerated in doses up to 50 mg/kg in cynomolgus monkeys. Here we report data 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 solid 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 year. 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 Taiwan. As of 28th Oct 2019, a total of 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 eight patients across all cohorts reached stable disease (SD).

Pharmacokinetics

PK profiles of HLX10 demonstrated a dose-proportional 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 [10.5%]).

Conclusion

•HLX10 was well-tolerated in patients with recurrent or metastatic solid tumors and elicited durable anti-tumor 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.