A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma

Abstract

Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-naïve, CD20-positive DLBCL patients aged 18-80 years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], − 3.59 to 6.32, p = 0.608) which falls within the pre-defined equivalence margin of ± 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%, p = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%, p = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at http:// www.chinadrugtrials.org.cn on 26 August 2015 [#CTR20150583].

Efficacy and Safety of ABP 798: Results from the JASMINE Trial in Patients with Follicular Lymphoma in Comparison with Rituximab Reference Product

“…Though not currently approved in the US, HLX01 (Shanghai Henlius Biotech Inc, Shanghai, China) has been evaluated in a comparative clinical study to assess the efficacy, safety, and immunogenicity of HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone compared with rituximab RP in the same combination dosing paradigm in patients with histologically confirmed CD20 + diffuse large B-cell lymphoma (Ann Arbor stages I-IV) every 21 days for up to six cycles. The primary efficacy endpoint of comparability of best ORR within six cycles of treatment was met [30].…”

The changing landscape of anti-lymphoma drug clinical trials in mainland China in the past 15 years (2005–2020): A systematic review

“…In February 2015, CDE of NMPA launched “Guidelines for the research, development and technique assessment of biosimilar drugs (Trial)”, which accelerated the development of biosimilar drugs in China [6] . Since HLX01, the first biosimilar of rituximab, has been approved by NMPA in 2019 [19] , the R&D of CD20 monoclonal antibody has become the hotspot for lymphoma. In March 2020, CDE asked public comments on “Guidelines of clinical trials in rituximab biosimilar drugs (the draft for comments)” [20] .…”

Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress

“…Indeed, upregulated CD25 expression is related to a more aggressive course and an inferior outcome in DLBCL, FL, HL, and CLL [ 103 – 106 ]. It has also been shown to promote lymphomagenesis and drug resistance in T cell lymphomas [ 107 ].…”