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First Patient Dosed in Australia for a Phase 2 International Clinical Trial of Henlius' PD-L1 ADC HLX43 for NSCLC

2025-09-19

  • To date, over 400 patients enrolled globally for HLX43, including more than 170 patients with NSCLC

  • Following China and the U.S, HLX43 completed the first patient dosing in Australia for the phase 2 MRCT in NSCLC, further advancing its global development

  • According to updated results at 2025 WCLC, HLX43 sustained superior efficacy with a favorable safety profile in expanded NSCLC cohorts, notably in the EGFR wild-type NSCLC subgroup, further underscoring its biomarker-independent therapeutic potential with exhibiting robust efficacy in PD-L1 negative patients


Shanghai, China, September 18, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject has been dosed in Australia for HLX43-NSCLC201, a phase 2 international muti-center clinical trial of HLX43, its innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC), for the treatment of patients with advanced non-small cell lung cancer (NSCLC). Henlius is vigorously advancing the global development of HLX43, with an international multi-region phase 2 clinical trial initiated in China, the US, Australia, and Japan, and finished first patients dosing of the phase 2 clinical trial in China, the US and Australia. At present, no PD-L1 targeting ADC has been approved for marketing globally. 


Lung cancer is the most common cancer worldwide in terms of incidence and mortality. According to GLOBOCAN 2022, there were over 2.48 million new cases of lung cancer globally in 2022, accounting for 12.4% of all new cancer cases [1]. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (approximately 85%). The majority of lung cancer patients are diagnosed at advanced stages with a poor five-year survival prognosis [2], highlighting a significant unmet clinical need. By histology, NSCLC can be classified into squamous cell carcinoma (approximately 30%), adenocarcinoma (approximately 50%) and other subtypes including large cell carcinoma. EGFR wild-type cases account for 70%-85% of all NSCLC patients, including nearly all squamous cell carcinoma cases and 50-55% of adenocarcinoma cases [3]. Currently, the treatment landscape of EGFR wild-type NSCLC remains limited by a scarcity of highly effective options, particularly in second-line and later (2L+) therapy, where docetaxel-based chemotherapy continues to serve as the standard of care despite its suboptimal efficacy [4,5].


HLX43 is a 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, 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/liver metastasis, and PD-L1 positive or negative patients.


According to updated data released at the 2025 WCLC, HLX43 continues to demonstrate superior efficacy in an expanded cohort of NSCLC patients, and highlights its therapeutic potential in specific subgroups such as EGFR wild-type NSCLC patients. Confirmed objective response rate (cORR) was 46.7% for patients with an EGFR wild-type non-squamous NSCLC. Among these patients, cORR was 60.0% for those receiving HLX43 at 2.5 mg/kg, along with a favorable safety profile. Notably, HLX43 exhibits robust efficacy in PD-L1 negative (TPS <1%) patients, with an ORR of 38.1% and disease control rate (DCR) of 85.7%, indicating its differentiated therapeutic potential to cover a broader patient population regardless of PD-L1 expression.


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. 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 a immunotherapeutic agent, and existing standard of care. 


In addition to NSCLC, Henlius is actively exploring HLX43's therapeutic potential in various solid tumors. The company has initiated 10 clinical studies for HLX43, covering thymic carcinoma (TC), cervical cancer (CC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), colorectal cancer (CRC), and gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.  Both monotherapy and combination therapies of HLX43 are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and other agents. HLX43 may benefit more patients with advanced or metastatic solid tumors by providing a novel treatment option for those who are unresponsive or have developed resistance to PD-1/PD-L1-targeted therapies, as well as the patients who have failed prior chemotherapy or TKI therapies.


By strategically prioritizing lung cancer 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】

[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.

[2] Robinson CG, et al. Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated with Adjuvant Chemotherapy: A Review of the National Cancer Data Base. Journal of Clinical Oncology 2015, 33(8): 870-876.

[3] Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015 Feb;4(1):36-54.

[4] 中国临床肿瘤学会 中国临床肿瘤学会(CSCO).(2024)非小细胞肺癌诊疗指南

[5] NCCN Guidelines Version 3. 2025, Non-Small Cell Lung Cancer.


About HLX43-NSCLC201

This is an open-label, multi-center, international phase 2 clinical study to evaluate HLX43 in patients with advanced non-small cell lung cancer (NSCLC). This study aims to evaluate the efficacy and safety of HLX43 in advanced non-small cell lung cancer (NSCLC) patients. It consists of two parts: Part 1, which focuses on dose exploration to identify the optimal HLX43 dosage for Part 2; and Part 2, which is a single-arm, multi-center phase 2 clinical trial. The primary objective of this study is to evaluate the clinical efficacy of HLX43 in advanced non-small cell lung cancer (NSCLC) patients. The primary endpoint of the study is objective response rate evaluated by the Blinded Independent Central Review (BICR) according to RECIST v1.1.