63P - A randomised, double-blind, phase I study to compare the pharmacokinetics, safety, tolerability, and immunogenicity of HLX15 and daratumumab in healthy male participants

Background

Daratumumab (anti-CD38 monoclonal antibody [mAb]) has been approved for multiple myeloma. However, the high cost and discrepancy in regulatory approval across geographical regions have limited its accessibility for patients globally. HLX15, a recombinant anti-CD38 fully human mAb, showed biosimilarity with daratumumab in preclinical studies. This first-in-human study aimed to evaluate the bioequivalence of HLX15 and daratumumab in healthy Chinese male participants.

Methods

This phase I study consisted of 2 parts. Part I was a single-centre, open-label, randomised, pilot study. Part II was a multicentre, randomised, double-blind, pivotal study to compare HLX15 with daratumumab and is presented below. Healthy Chinese male participants aged 18–60 years were enrolled and randomised 1:1:1:1 to receive a single intravenous infusion of HLX15 (group A), China-sourced daratumumab (group B), US-sourced daratumumab (group C), or European Union-sourced daratumumab (group D) at 8 mg/kg. Primary endpoint was the area under the serum concentration-time curve from time 0 to infinity (AUC_0-inf). Secondary endpoints included other pharmacokinetic (PK) parameters, safety, and immunogenicity.

Results

Of the 172 participants enrolled in part II (43 per group), 165 (group A, n=41; group B, n=41; group C, n=42; group D, n=41) were included in the PK analysis. The geometric mean ratio and its 90% confidence intervals for primary endpoint AUC_0-inf between any two groups were within the predefined equivalence margin of 80.00–125.00%, indicating PK similarity between HLX15 and the reference daratumumab. Other PK parameters were also comparable. Treatment-emergent adverse events (AEs), treatment-related AEs and AEs of special interest were mostly mild (grade 1 to 2) and similar across all groups. The overall positive rate of anti-drug antibody was also comparable across the groups with no neutralizing antibody being detected.

Conclusions

PK similarity between HLX15 and daratumumab from different regions was demonstrated, along with comparable safety and immunogenicity profiles. HLX15 is a promising biosimilar of daratumumab that warrants further investigation.

Clinical trial identification

NCT05679258 (released on 10 January 2023).

Editorial acknowledgement

Abstract writing support was provided by Zhi Hao Kwok, and Chen Hu of Shanghai Henlius Biotech, Inc.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

C. Sun, H. Yu, Q. Wang: Financial Interests, Institutional, Full or part-time Employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.