HLX07 is a recombinant, humanized anti-epidermal growth factor (EGFR) antibody manufactured in Chinese Hamster Ovary (CHO) cells. The re-engineered antibody binding fragment (Fab) of HLX07 is designed for improved binding affinity to EGFR and decreased immunogenicity. Preclinical studies have shown in vivo anti-tumor activity of HLX07 at equivalent or increased potency of cetuximab. Here we report latest findings from a Phase 1 study (NCT02648490) of HLX07 in advanced solid tumors at the 2019 ESMO-Asia congress in Singapore.

Study Design

We conducted a prospective, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics(PK) and efficacy of HLX07 in patients with advanced solid tumors who have failed standard therapy or for whom no therapy is available. The study employed a traditional 3+3 dose escalation design, with a minimum of three patients enrolled at each dose level. Patients received once-weekly infusion of HLX07 at doses of 50, 100, 200, 400, 600 and 800mg until disease progression, study withdrawal or death (whichever occurred first). Dose-limiting toxicities (DLTs) were evaluated over 28 days following the first dose, with radiological assessment of treatment responses every 8 weeks.

Results

The clinical trial was conducted in Taiwan. As of 13th June, 2019, a total of 19 patients were enrolled. 84.2% of patients were male with a median age of 58 years.

Efficacy

Among 17 evaluable patients, one patient in the 600mg cohort achieved a partial response (PR) and five patients across all cohorts had reached stable disease (SD).

Pharmacokinetics

PK parameters demonstrated dose-dependent manner with each escalated dose of HLX07.

Safety

HLX07 was well tolerated at all dose levels up to 800mg with no dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) was not reached. No new safety signals were identified across 6 cohorts.

Conclusion

•HLX07 was well tolerated at all dose levels up to 800mg, with no DLT and MTD was not reached.

•HLX07 showed desirable anti-tumor effect: among 17 patients available for evaluation, one achieved PR and five achieved SD.

•These findings supported the development of a Phase 1b/2 study of HLX07 to further evaluate its safety and efficacy combined with different chemotherapy regimens in the treatment of patients with advanced solid tumors (NCT03577704).