Shanghai, China, May 16, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject was dosed for a phase 1/3 clinical trial of the company's independently developed ipilimumab biosimilar HLX13 (recombinant anti-CTLA-4 fully human monoclonal antibody injection) in China. In April 2025, Henlius entered into a license agreement with Sandoz, granting Sandoz the exclusive commercial rights for HLX13 in the United States, 42 European countries and regions, Japan, Canada, and Australia.
Immune checkpoint inhibitors are playing a crucial part in immunotherapy, which has emerged in recent years as a novel approach to combating tumour cells with distinct advantages and enormous promise [1]. In addition to PD-1/L1 and LAG-3, CTLA-4 is also an inhibitory immune checkpoint which expressed on regulatory T cells and activated T cells and has a higher affinity to B7 molecules compared with CD28, thus can competitively bind to B7 molecules to inhibit the proliferation and activation of T cells [2]. Anti-CTLA-4 fully human monoclonal antibody (mAb) can block the inhibitory effects of CTLA-4 on the co-stimulation signal necessary to T cell activation and can increase the number of reactive T-effector cells which mobilize to mount a direct T-cell immune attack against tumour cells. Also, anti-CTLA-4 mAb may selectively deplete T-regulatory cells at the tumour site, leading to an increase in the intratumoral T-effector/T-regulatory cell ratio which drives tumour cell death. Meanwhile, results showed that the combination therapy of anti-CTLA-4 mAb and anti-PD-1 mAb is expected to have a synergistic effect and may bring additional clinical benefit to patients [3-4]. Currently, ipilimumab has been approved in various countries and regions in combination with nivolumab for the treatment of melanoma and hepatocellular carcinoma, among other indications.
HLX13 is a biosimilar of ipilimumab independently developed by Henlius in accordance with the NMPA, EMA, FDA and other international biosimilar guidelines. The indications to be developed for HLX13 are solid tumours. Henlius has conducted a series of head-to-head pre-clinical studies to compare the chemical manufacture and control (CMC), pharmacology, toxicity, and pharmacokinetics profiles of HLX13 and originator ipilimumab. Results from these studies showed that there is a high similarity or no significant difference between HLX13 and originator ipilimumab.
Looking forward, Henlius will continue to focus on unmet clinical needs and bring more high-quality, affordable and innovative therapeutic solutions to patients around the world by giving full play to the company's integrated platform advantages in the field of antibody drugs and antibody-drug conjugates, and by continuing to explore the therapeutic potential of immunotherapy in oncology field.
About NCT06841185
This study is a multicentre, randomized, double-blind, parallel-controlled Phase 1/3 clinical study to evaluate the similarity of pharmacokinetic (PK) profiles, efficacy, safety, and immunogenicity among HLX13 and its reference product YERVOY® (US-sourced and EU-sourced) as treatment for patients with unresectable advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy. Eligible subjects will be randomized in a 2:1:1 ratio to receive HLX13, US-sourced YERVOY® or EU-sourced YERVOY®. During the initial 4 treatment cycles, subjects across all study groups received the investigational product every 3 weeks in combination with nivolumab. Thereafter, nivolumab is administered every 4 weeks for up to 10 cycles. The primary PK endpoints are the area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d) and the area under the serum concentration-time curve within a dosing interval at steady state (AUCss). The primary efficacy endpoint is the best objective response rate (ORR) assessed by the Independent Radiology Review Committee (IRRC) as per Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1) up to Week 24. Secondary endpoints include other PK parameters, other efficacy assessments, safety, and immunogenicity.
