Shanghai, China, April 9, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject has been dosed for a phase 1b/2 clinical trial of HLX43 for Injection, the novel Programmed Death-Ligand 1 (PD-L1)-targeting antibody-drug conjugate (ADC) that developed by the company based on the collaboration with MediLink Therapeutics, in combination with the Henlius' independently developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab injection), for the treatment of patients with advanced/metastatic solid tumours in Chinese mainland. Recently, the company has also completed the first subject dosing for a phase 2 clinical trial of HLX43 for monotherapy or combination therapy to treat patients with advanced/metastatic solid tumours. At present, no PD-L1 targeting ADC has been approved for marketing globally, and only SGN-PDL1V from Pfizer is about to initiate a phase 3 clinical trial. HLX43 is the world's second and China's first PD-L1-targeting ADC to progress to clinical research.
Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have emerged in recent years and revolutionised all lines of treatment for tumour patients. However, there are still many patients with positive PD-L1 expression who do not respond to or develop resistance to PD-1/PD-L1-targeted therapy [1]. To date, there has been no subsequent-line treatment for patients who are resistant to PD-1/L1 immunotherapy or failed to benefit from the standard treatments including immunotherapy, indicating a significant unmet medical need to further improve the clinical benefits for these patients. As a novel targeting therapy with the most prominent anti-tumour efficacy, ADCs have shown preliminary therapeutic potential in the treatment of multiple advanced solid tumours, such as breast cancer (BC), lung cancer (LC), esophageal cancer (EC) and gastric cancer (GC), making it a promising therapeutic in solid tumours [2]. PD-L1 is expressed in patients across a broad spectrum of tumour types including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), triple negative breast cancer (TNBC), squamous cell carcinoma and displays limited expression on normal tissues, highlighting the potential of PD-L1 as a target for ADCs, which may bring new options for cancer treatment [3].
Combining the selectivity of targeted monoclonal antibodies with the highly potent cytotoxic agent, HLX43 could exert anti-tumour effects through specific binding to the PD-L1 expressed on the surface of tumour cells and release cytotoxic payloads after internalisation by the cancer cells. The cytotoxic payload of HLX43 is a novel DNA topoisomerase-I inhibitor which are known for their potent anti-tumor activity, shorter half-life in the bloodstream, and improved safety profile [4]. This next generation design allows HLX43 to possess a higher therapeutic index and potency for treatment of solid tumours. Several non-clinical studies and the phase 1 clinical trial have shown that, HLX43 has good anti-tumour effects and a favorable tolerability profile in non-small cell lung cancer (NSCLC), and other tumour types that were PD-1/L1 mAb-resistant. The results of the pre-clinical studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Based on these compelling results, Henlius has initiated phase 2 clinical trials of HLX43 in potential solid tumour indications including ESCC 安定other solid tumours to further evaluate the efficacy and safety of HLX43. While accelerating the development of ADCs and diversified drug conjugates, Henlius is also actively exploring combination therapies involving ADCs with immunotherapy to encourage progress in the next wave innovation of “IO+ADC”, further providing more effective treatment options to fulfill the unmet clinical needs.
Moving forward, Henlius remains committed to addressing unmet medical needs by leveraging its antibody drug R&D platform, actively driving the development of innovative therapies to deliver high-quality and affordable treatment options to patients worldwide.
About HLX43HLX10-ST201
This phase 1b/2 study aims to evaluate the safety, tolerability, and efficacy of HLX43 in combination with HANSIZHUANG in patients with advanced/metastatic solid tumors. The study is divided into two stages: phase 1b dose escalation and phase 2 dose expansion. Eligible subjects will receive intravenous infusions of different doses of HLX43 combined with a fixed dose of HANSIZHUANG every three weeks (Q3W). The second stage is a multicenter, randomized, open-label controlled study to evaluate the safety and efficacy of three different doses of HLX43 combined with a fixed dose of HANSIZHUANG in patients with advanced non-small cell lung cancer (NSCLC) based on data from the first stage. The primary endpoints of the first stage are the proportion of subjects experiencing dose-limiting toxicity (DLT) events in each dose group during the DLT observation period and the maximum tolerated dose (MTD) of HLX43 in combination with HANSIZHUANG. The primary endpoint of the second stage is the objective response rate (ORR) assessed by the Independent Radiological Review Committee (IRRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
References
[1] Attili I, et al. Strategies to overcome resistance to immune checkpoint blockade in lung cancer[J]. Lung cancer: Journal of the International Association for the Study of Lung Cancer, 2021(154-):154.
[2] He J, Zeng X, Wang C, Wang E, Li Y. Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies. MedComm (2020). 2024 Jul 28;5(8):e671.
[3] Kwan B, et al. 783 SGN-PDL1V, a novel, investigational PD-L1-directed antibody-drug conjugate for the treatment of solid tumors[J]. 2021.
[4] Conilh, L, et al. Payload diversification: a key step in the development of antibody–drug conjugates. J Hematol Oncol 16, 3 (2023).
