Henlius Advances Triple-Combination Cancer Therapy with NMPA Approval for HLX43 ADC Study
核心洞察
Shanghai Henlius Biotech (搜索) received NMPA approval for a clinical trial combining its PD-L1 (搜索)-targeting ADC HLX43 with anti-PD-1 (搜索) antibody serplulimab and anti-EGFR (搜索) antibody HLX07 for advanced solid tumors (搜索).
The triple-combination strategy aims to harness synergistic effects of dual immune checkpoint blockade and precision targeting to overcome treatment resistance and address unmet clinical needs.
HLX43 demonstrates dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity, with preliminary clinical data showing manageable safety and encouraging efficacy across various solid tumors.
Shanghai Henlius Biotech (搜索) has received approval from China's National Medical Products Administration (NMPA) to begin clinical trials of an innovative triple-combination cancer therapy, marking a significant advancement in the company's solid tumor treatment pipeline. The investigational new drug application for HLX43, a programmed death-ligand 1 (PD-L1 (搜索)) targeting antibody-drug conjugate, in combination with serplulimab (HANSIZHUANG (搜索)) and HLX07 has been approved for treating advanced solid tumors (搜索).
Strategic Combination Approach
The approved triple-combination regimen represents an evolution from Henlius's ongoing dual-combination strategies. The company has been conducting clinical trials of HLX43 combined with serplulimab, as well as HLX43 combined with HLX07, and now plans to expand into the triple-combination approach to maximize clinical value through synergistic effects.
Immune checkpoint inhibitors, particularly anti-PD-1 (搜索)/PD-L1 (搜索) monoclonal antibodies, have become cornerstone cancer treatments. However, many patients do not respond to or derive limited benefit from monotherapy, driving the development of combination strategies. Antibody-drug conjugates have emerged as highly effective options for combination with immunotherapy, potentially creating synergy for more potent and durable responses while overcoming resistance.
Key Components of the Combination
HLX43 serves as the foundation of this approach as a potentially best-in-class pan-tumor ADC candidate targeting PD-L1 (搜索). The drug exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Preliminary clinical data has indicated a manageable safety profile and encouraging efficacy in various solid tumors, with notable anti-tumor activity observed in various non-small cell lung cancer (搜索) patient subgroups.
Serplulimab (HANSIZHUANG (搜索)) brings proven clinical success as the world's first and only anti-PD-1 (搜索) monoclonal antibody to succeed in a phase 3 registration study for perioperative gastric cancer (搜索). It is also the first anti-PD-1 antibody approved for first-line treatment of small cell lung cancer (搜索). The drug has been approved in over 40 countries and regions, covering nearly half of the global population.
HLX07 represents Henlius's innovative anti-EGFR (搜索) monoclonal antibody development. Compared with cetuximab, HLX07 demonstrates lower immunogenicity and higher target affinity. Recent clinical data from the 2025 World Conference on Lung Cancer showed that the combination of HLX07 with serplulimab and chemotherapy demonstrated remarkable antitumor activity as first-line treatment for patients with EGFR overexpression squamous non-small cell lung cancer (搜索).
Clinical Evidence Supporting the Approach
The rationale for targeting EGFR (搜索) stems from its role as a crucial driving mechanism in various malignant tumors, including lung cancer, colorectal cancer (搜索), and head and neck squamous cell carcinoma (搜索). EGFR overexpression establishes it as one of the validated key targets in solid tumor treatment. However, abnormal EGFR activation can lead to immune evasion and create an immunosuppressive microenvironment, resulting in limited efficacy for single agent targeted therapy.
Clinical data for HLX07 plus serplulimab with chemotherapy showed impressive results in EGFR (搜索) overexpression squamous non-small cell lung cancer (搜索) patients. At a median follow-up of 18.6 months, both dose groups achieved an objective response rate of around 70% and a disease control rate of over 90%. The median progression-free survival reached 17.4 months in the high-dose group.
Parallel Development of Bispecific Innovation
Concurrently, Henlius announced the first patient dosing in a phase 1 clinical trial for HLX37, an innovative recombinant humanized anti-PD-L1 (搜索) and anti-VEGF (搜索) bispecific antibody. This first-in-human study marks the initiation of clinical development for HLX37 in patients with advanced/metastatic solid tumors in China.
HLX37's mechanism of action integrates two therapeutic pathways: blocking PD-1 (搜索)/PD-L1 (搜索) interaction to reverse tumor-induced immunosuppression and neutralizing VEGF (搜索) to suppress tumor angiogenesis. By specifically binding to PD-L1 on tumor cells, HLX37 achieves enhanced enrichment within the tumor microenvironment, potentially leading to superior efficacy compared to combination anti-PD-L1 and anti-VEGF monoclonal antibodies.
Platform-Driven Innovation
The development of these advanced therapeutics reflects Henlius's integrated antibody discovery-to-manufacturing platform. The platform focuses on function-blocking antibodies and features robust, diversified VHH libraries encompassing natural, synthetic humanized, and immunized llama VHHs. This enables efficient selection of high-affinity and highly specific VHHs and scFvs against diverse targets.
The company has systematically developed a comprehensive discovery and characterization database for multispecific antibodies, including bispecific, trispecific, and tetraspecific formats, as well as antibody fusion proteins. Built upon this platform, Henlius has advanced 10 products to marketing approval while fostering a pipeline of 19 clinical-stage assets with over 30 clinical studies ongoing.
Clinical Trial Design
The HLX37-FIH101 study is an open-label, first-in-human Phase I clinical trial evaluating safety, tolerability, pharmacokinetic profiles, and preliminary efficacy of HLX37 in subjects with advanced/metastatic solid tumors. The study consists of Phase Ia dose escalation and Phase Ib dose expansion phases. The Phase Ia monotherapy arm evaluates 6 dose levels ranging from 1.0 mg/kg to 45.0 mg/kg administered every three weeks, while the combination therapy arm will explore different doses of HLX37 with pemetrexed or albumin-bound paclitaxel/paclitaxel and carboplatin in advanced non-small cell lung cancer (搜索) patients.