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Updated key results for HLX43 in lung cancer released, marking the first combined results from the Phase 2 MRCT in NSCLC, reinforce global clinical profile of the product
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HLX43 demonstrates dual potential as both a best-in-class and best-in-disease candidate, promising to offer breakthrough treatment options for lung cancer patients
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HLX43 received Orphan Drug Designation from the U.S. FDA for TETs; POC data in CC and ESCC are expected soon, continuous to unleashing broad product value
Shanghai, China, November 2, 2025 – Henlius (2696.HK) presented updated key data for its PD-L1 antibody-drug conjugate (ADC) HLX43 in patients with non-small cell lung cancer (NSCLC) at the "2025 International Summit on Frontiers and Innovation in Lung Cancer ". This marks the first time to incorporate results from the multi-regional phase 2 clinical study of HLX43, highlighting the efficacy and safety of the product at the recommended phase 2/3 dose (RP2/3D). The updated findings further validate the promising efficacy of HLX43 in NSCLC, as well as its clinical value across broader patient populations.
HLX43 is a potential best-in-class as well best-in-disease broad-spectrum anti-tumor ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Preclinical data have shown that, HLX43 has good anti-tumor effects and a favorable tolerability profile in NSCLC, cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumor types that were PD-1/L1 mAb-resistant. The results from the phase 1 clinical trial of HLX43 has been first released at the 2025 ASCO Annual Meeting and 2025 WCLC, demonstrating manageable safety profile and encouraging efficacy in various solid tumors especially in patients with NSCLC, including squamous and non-squamous NSCLC patients (sqNSCLC and nsqNSCLC), patients with or without EGFR mutation, patients with or without brain metastasis, and PD-L1 positive or negative patients.
Pooled Analysis at RP2/3D in NSCLC Underpins Global Development Potential of HLX43
Based on the results of prior dose exploration, we prospectively identified 2.0 mg/kg or 2.5 mg/kg as the recommended phase 2/3 dose (RP2/3D) for HLX43 in patients with NSCLC. The updated data released focused on the efficacy and safety of HLX43 the at RP2/3D. This pooled analysis, which included 174 NSCLC patients who received either 2.0 mg/kg or 2.5 mg/kg Q3W intravenous dosing from two studies, HLX43-FIH101 and HLX43-NSCLC201, aiming to systematically evaluate the efficacy and safety of HLX43 at the RP2/3D, providing a core foundation for decision-making in subsequent pivotal clinical trials.
HLX43-FIH101 is an open-label, first-in-human (FIH) phase I clinical trial conducted in China to evaluate the safety, pharmacokinetics, and preliminary efficacy of HLX43 in patients with advanced/metastatic solid tumors. The study included a dose-escalation phase (phase 1a) to determine the maximum tolerated dose (MTD) across 0.5-4.0 mg/kg, and a dose-expansion phase (phase 1b) focusing on patients with advanced or metastatic NSCLC who had failed standard therapy, evaluating doses from 2.0-3.0 mg/kg to determine the recommended phase 2 dose (RP2D). HLX43-NSCLC201 is an open-label, multi-center international phase 2 clinical trial evaluating the efficacy and safety of HLX43 in patients with advanced NSCLC who had failed at least one prior line of standard therapy. The study is divided into a dose-selection phase (Part A) and a dose-expansion phase (Part B), with the primary endpoint being objective response rate (ORR) as assessed by a blinded independent central review (BICR) per RECIST v1.1.
Updated Key Efficacy Data (including subgroup analysis)
As of October 22, 2025, the pooled analysis included 174 patients with advanced NSCLC. Among them, 89 patients received intravenous HLX43 at 2.0 mg/kg, and 85 patients received 2.5 mg/kg. All enrolled patients (100%) had previously received platinum-based therapy. Approximately 80% and over 30% of patients had previously received immunotherapy and targeted therapy, respectively. Some patients had received docetaxel.
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Significant Efficacy in Overall Population: HLX43 demonstrated significant efficacy across the overall NSCLC population. In sqNSCLC patients receiving 2.0 mg/kg (n=33) HLX43, the investigator-assessed ORR was 33.3%, with a disease control rate (DCR) of 75.8%. Efficacy was more notable in non-squamous NSCLC patients(including EGFR wild type& EGFR mutant) receiving 2.5 mg/kg (n=35), where the ORR reached 48.6% and the DCR was 94.3%
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Superior Efficacy in Docetaxel-Treated Patients: In sqNSCLC patients who had received prior docetaxel treatment (third line or later, n=13), HLX43 achieved an ORR of 38.5% and a DCR of 84.6%, suggesting its important potential in sqNSCLC patients who have failed docetaxel treatment
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Enhanced Benefit in Non-Squamous NSCLC: ORR was 48.6%, with a DCR of 94.3% in nsqNSCLC population (2.5mg/kg, n=35). Notably, ORR was 47.4% for patients with an EGFR wild-type nsqNSCLC (n=19). While in patients with EGFR-mutant nsqNSCLC (n=16), HLX43 received an ORR of 50.0% and a DCR of 93.8%, highlighting superior efficacy of HLX43 in the nsqNSCLC subgroup
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Effective in Brain Metastases: In advanced NSCLC patients with brain metastasis (n=10), HLX43 still delivered significant clinical benefits, with a confirmed ORR (cORR) of 30.0% and DCR of 90.0%
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Efficacy Regardless of PD-L1 Status：Moreover, HLX43 exhibits rubust efficacy in PD-L1 negative (TPS <1%, n=43) patients, with a ORR of 39.5% and DCR of 86.0%, indicating its differented therapeutic potential to cover a broader patient population regardless of PD-L1 expression.
Updated Safety Data
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In terms of safety, the most common grade ≥3 TRAEs were lymphocyte count decreased (9.8%), anemia (8.6%), and neutrophil count decreased (6.3%). Platelet count decreased was reported in 1.7% of all treated patients. HLX43 continued to demonstrate low hematological toxicity, supporting its potential for expansion into first-line setting and combination therapies
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Immune-related AE was reported in 17 (9.8%) patients. Immune-mediated lung disease was reported in 5 (2.9%) patients, all of whom are in recovery
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In these patients with immune-mediated lung disease, the cORR was 40.0% and 100% tumor shrinkage was observed, highlighting the immunotherapeutic effects of HLX43 in addition to its payload-mediated cytotoxic tumor cell killing
Dual-Best Potential Fuels Broad-Spectrum Layout and Clinical Value Realization
The favorable clinical profile of HLX43 originates from its precision design and multiple innovation mechanisms. Compared to ADCs that target driver mutations, HLX43 engages the pan-tumor target PD-L1, demonstrating biomarker-independent and broad-spectrum anti-tumor potential. Its antibody backbone is derived from Henlius's proprietary anti-PD-L1 antibody, HLX20, ensuring high antigen binding and efficient tumor cell internalization. The cleavable linker-payload is licensed from MedLink’s TMALIN® platform, enables cytotoxic release both intracellularly post-internalization and within the tumor microenvironment. This unique payload release mechanism underpins the molecule's dual mechanism of action, which combines targeted ADC cytotoxicity with immune checkpoint blockade, positioning HLX43 as a promising best-in-class and best-in-disease candidate.
In 2023, HLX43 received IND approvals from both the China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA) to initiate clinical trials. The company is currently accelerating the clinical development of HLX43. To date, over 400 patients enrolled globally for HLX43, including more than 170 patients with NSCLC. Patient enrollment is progressing steadily across multiple countries including China, the U.S., and Japan. Notably, an international multi-center phase 2 clinical trial in NSCLC is currently being conducted simultaneously in China, the U.S., Japan, Australia, etc. As HLX43's efficacy validated in later-line treatment of NSCLC, Henlius plans to initiate a second-line clinical trial featuring a head-to-head comparison between HLX43 and docetaxel. Furthermore, based on the low toxicity and immuno-oncology (IO) activity demonstrated by HLX43, the company will actively explore and promote the first-line treatment regimens for HLX43, by conducting a three-arm clinical trial that includes monotherapy, combination therapy with an immunotherapeutic agent, and existing standard of care. Meanwhile, as the first PD-L1 ADC developed for thymic carcinoma globally, HLX43 is advancing its international multi-center clinical trials concurrently in China, the U.S., Japan, Australia, etc. In October 2025, based on the compelling preliminary efficacy data from later-line settings in thymic carcinoma (TC), the U.S. FDA granted Orphan Drug Designation (ODD) to HLX43 for the treatment of Thymic epithelial tumors (TETs), highlighting the drug's potential to address the significant unmet need for ADC therapies in this disease.
In addition to NSCLC and TC, Henlius is actively exploring HLX43's therapeutic potential in various solid tumors. The company has initiated 10 clinical studies for HLX43, covering CC, ESCC, head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), colorectal cancer (CRC), gastric or gastroesophageal junction (G/GEJ) adenocarcinoma and hepatocellular carcinoma (HCC). Proof-of-concept (PoC) data in CC and ESCC are expected to be released in the near future, which will add a critical piece to its broad-spectrum antitumor profile. Building on its intrinsic immuno-oncology (IO) activity, Henlius is exploring combination therapies, such as with the in-house anti-EGFR antibody HLX07, to maximize HLX43's clinical value.
Moving forward, Henlius remains committed to advancing the treatment landscape for lung cancer. By leveraging our core innovative pipeline including HLX43, we will amplify their differentiated therapeutic profile, expedite clinical value delivery, and expand breakthrough treatment options for global patients.