Shanghai, China, December 4, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for a phase 1b/2 clinical trial of HLX43 for Injection, the antibody-drug conjugate (ADC) product that developed by the company based on the collaboration with MediLink Therapeutics, has been approved by the China National Medical Products Administration (NMPA), for monotherapy or combination therapy to treat patients with advance/metastatic solid tumours. In November 2023, a phase 1 clinical trial of HLX43 has completed dosing its first subject, making it the first PD-L1-targeting ADC in China to enter a clinical trial. At present, no PD-L1 targeting ADC has been approved for marketing globally.
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]. 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[2]. 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 for this patient population. ADCs and ADCs combining immunotherapies are promising therapeutic strategies to further improve the clinical benefits for patients.
HLX43 is one of the first ADC candidates of Henlius to enter into clinical development. It is designed to address the issues of unresponsiveness or resistance to PD-1/L1 immunotherapies to fulfill the unmet medical needs of advanced/metastatic patients. 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. Up to date, HLX43 has exhibited good anti-tumour effects and a favorable safety profile in nonclinical pharmacology, pharmacokinetic studies and safety evaluation. The results of the studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Meanwhile, in a phase 1 clinical trial aims to evaluate the safety, tolerability and pharmacokinetics of HLX43 in patients with advanced/metastatic solid tumours, when the administration dose of HLX43 has been escalated to 4.0 mg/kg, every 3 weeks by intravenous infusion, it was well tolerated by patients. And patients with solid tumours (including non-small cell lung cancer, cervical cancer, etc.) who have progressed after prior standard treatment also respond to HLX43 treatment. Therefore, the company plans to initiate a phase 1b/2 clinical trial to explore the efficacy and safety of HLX43 monotherapy or HLX43 combination therapy in a variety of solid tumours patients who failed standard treatment, further validating the efficacy and safety of the product in broader patient population.
With a particular focus on addressing the unmet medical needs, Henlius will further take efforts to promote the layout of our innovative portfolio based on the company’s competitive edge of an integrated antibody drug R&D platform, bringing more high-quality and affordable therapeutics for patients worldwide.
【Reference】
[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] Kwan B, et al. 783 SGN-PDL1V, a novel, investigational PD-L1-directed antibody-drug conjugate for the treatment of solid tumors[J]. 2021.