Shanghai, China, September 30, 2025—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 innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC), in combination with the company's independently developed innovative anti-EGFR monoclonal antibody (mAb) HLX07, has been approved by the China National Medical Products Administration (NMPA), for the treatment of advanced/metastatic solid tumors. This represents the second combination therapy developed for HLX43.
HLX43 is a potential best-in-class PD-L1-targeted ADC, which is composed of a fully humanized anti-PD-L1 IgG1 antibody, a novel tripeptide linker and topoisomerase inhibitor payload. The drug-to-antibody ratio (DAR) is around 8. Preclinical data have shown that, HLX43 exerts potent anti-tumor effects with a favorable tolerability profile in non-small cell lung cancer (NSCLC), cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumor types that were PD-1/L1 mAb-resistant. In early-stage clinical trial, HLX43 demonstrates promising broad-spectrum antitumor activity with a favorable safety profile. It mediates a dual mechanism of action integrating immune checkpoint inhibition with targeted cytotoxic payload delivery, and exhibits efficacy independent of PD-L1 expression status. Updated 2025 WCLC data confirms its outstanding anti-tumor efficacy in an expanded cohort, particularly in subgroups such as EGFR wild-type NSCLC, where a confirmed objective response rate (cORR) was 46.7% for EGFR wild-type non-squamous NSCLC, and 60.0% for those receiving HLX43 at 2.5 mg/kg.
HLX07 is an innovative anti-EGFR mAb developed by Henlius. Compared with cetuximab, HLX07 demonstrates lower immunogenicity and higher target affinity. Fc engineering extends its half-life, enabling every-3-week dosing that facilitates combination with immuno-oncology agents. Preclinical studies showed synergistic antitumor activity of HLX07 with the anti-PD-1 mAb serplulimab across tumor models [1]. Accordingly, Henlius is conducting phase 2 clinical trials to explore HLX07 as monotherapy or in combination with serplulimab for the treatment of solid tumors including squamous non-small cell lung cancer (sqNSCLC), cutaneous squamous cell carcinoma (CSCC), nasopharyngeal carcinoma (NPC) and ESCC.
According to the updated results in 2025 WCLC, the combination of HLX07 with serplulimab and chemotherapy demonstrated remarkable antitumor activity and durable efficacy as first-line treatment for patients with EGFR overexpression sqNSCLC. At a median follow-up of 18.6 months, both dose groups achieved an objective response rate (ORR) of around 70% and a disease control rate (DCR) of over 90%. The median progression-free survival (PFS) reached 17.4 months in the high-dose group. The median progression-free survival (PFS) in the low-dose group has not yet been reached, as most patients continue to exhibit stable disease, underscoring the enduring treatment effect.This indicates that the combination of HLX07 and serplulimab blocks EGFR signaling while activating immune responses, supporting strong therapeutic synergy.
Studies have demonstrated that the combination of cetuximab and irinotecan (a topoisomerase inhibitor) is superior to either agent alone in metastatic colorectal cancer (mCRC)[2]. This combination is approved for both first-line and later-line treatment of mCRC[3-4]. Furthermore, this "anti-EGFR antibody plus chemotherapy" strategy is now widely used for various solid tumors, including colorectal, head and neck squamous cell carcinoma (HNSCC), and pancreatic cancers[4-6].
Therefore, HLX43 integrates the immuno-oncology (IO) activity of an anti-PD-L1 mAb with the targeted cytotoxicity of a topoisomerase inhibitor, potentially synergizing with the anti-EGFR mAb HLX07 to demonstrate superior efficacy over conventional topoisomerase inhibitor plus anti-EGFR antibody regimens, thereby providing enhanced clinical benefits for patients with advanced solid tumors.
Currently, Henlius is vigorously advancing the clinical development of HLX43, with its therapeutic potential currently being explored across 10 clinical studies in various solid tumors, including NSCLC, thymic carcinoma (TC), CC, hepatocellular carcinoma (HCC), ESCC, head and neck squamous cell carcinoma (HNSCC), NPC, colorectal cancer (CRC), and gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Among these, the multi-regional clinical trials (MRCTs) of HLX43 in NSCLC and TC and other solid tumors have been initiated across China, the U.S., Australia and Japan. Based on the promising immuno-oncology (IO) effect demonstrated by HLX43, a phase 1b/2 clinical trial to evaluate its combination therapy with serplulimab in patients with solid tumors is underway. Furthermore, the company is actively exploring the therapeutic potential of HLX43 in combination with other agents to fully maximize its clinical value.
By strategically prioritizing solid tumor domain as a core therapeutic area, Henlius continues to uphold its patient-centric mission, accelerating differentiated innovation to address unmet medical needs and delivering high-quality, affordable therapies to tumor patients worldwide.
【Reference】
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