On May 27, 2026, Henlius (2696.HK) announced that the first patient has been dosed in China in the phase 2/3 international multicentre clinical trial (HLX43-NSCLC302) evaluating the company’s innovative PD-L1 ADC HLX43 for the treatment of patients with previously treated advanced/metastatic squamous non-small cell lung cancer (sqNSCLC), marking the official initiation of the study in the country. Recently, the study also received tacit approval from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). The trial will be conducted across multiple countries, including China, the United States, and Japan. The phase 3 stage is expected to serve as the first pivotal registration study for HLX43 and represents a significant milestone for HLX43 in the field of NSCLC, poised to offer a new therapeutic option for refractory sqNSCLC patients who have progressed on prior standard therapies.
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 2022.1 Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer (approximately 85%). By histology, NSCLC can be classified into squamous cell carcinoma (approximately 30%), adenocarcinoma (approximately 50%) and other subtypes, with a generally poorer prognosis for sqNSCLC.2 While immune checkpoint inhibitors (ICIs) combined with chemotherapy have significantly improved survival in advanced/metastatic sqNSCLC, effective options remain limited for patients progressing after first-line therapy. The current second-line and later-line treatment landscape is dominated by docetaxel-based regimens, with few agents demonstrating superior efficacy, highlighting a substantial unmet medical need.3-4 In recent years, antibody-drug conjugates (ADCs) have demonstrated favorable clinical efficacy in oncology, with promising activity observed in the later-line treatment of sqNSCLC.5-6 Separately, anti-EGFR monoclonal antibodies combined with chemotherapy have achieved progress in sqNSCLC, albeit primarily in EGFR-high expressing populations.7-9 The efficacy of novel therapeutic regimens incorporating anti-EGFR monoclonal antibodies in patients with low EGFR expression remains an area requiring further exploration.
HLX43 is a potentially best-in-class pan-tumour ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Currently, it has demonstrated a manageable safety profile and encouraging efficacy in various solid tumours, with notable anti-tumour activity observed in multiple NSCLC patient subgroups. According to the abstract of the HLX43 monotherapy study for NSCLC presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, among the 161 response‑evaluable patients (2, 69, 64, 21, and 5 in the 1, 2, 2.5, 3, and 4 mg/kg groups, respectively), the investigator‑assessed ORR was 31.1%. Among patients with EGFR wild-type non-squamous NSCLC (n=19), HLX43 has shown preliminary clinical advantages, with an ORR of 47.4%. For patients who had previously failed docetaxel (n=15), the ORR still reached 40.0%. Biomarker exploratory analyses showed that efficacy was not associated with PD‑L1 expression, with ORRs of 30.1% and 32.1% in patients with PD‑L1‑positive (n=83) and PD‑L1‑negative tumours (n=78), respectively. Overall, 199 (97.1%) patients experienced treatment-related adverse events (TRAEs), of whom 88 (42.9%) had grade ≥3 in severity. Most common Grade ≥3 TRAEs (incidence ≥10%) included lymphocyte count decreased (n=47, 22.9%), white blood cell count decreased (n=27, 13.2%), anaemia (n=25, 12.2%), and neutrophil count decreased (n=23, 11.2%). TRAEs led to treatment discontinuation in 17 (8.3%) patients. The full data will be formally released as a Rapid Oral Presentation on the afternoon of May 30 (CDT). Notably, the presentation will include the first disclosure of subgroup PFS data, further evaluating the clinical potential and therapeutic value of HLX43 in the treatment of relapsed/refractory NSCLC.
Pimurutamab is a humanized anti-EGFR mAb developed by Henlius, featuring reduced immunogenicity and enhanced binding affinity to the EGFR target. Through Fc engineering, pimurutamab demonstrates a significantly prolonged half-life, and the 3-week dosing frequency makes it more suitable for clinical use in combination with immunotherapies. Preclinical trials have shown that, compared with existing anti-EGFR mAbs, pimurutamab exhibits improved biological activity, significantly inhibiting tumour cell growth across multiple tumour models. HLX43 is thus expected to synergize with the anti-EGFR mAb pimurutamab. This combination has the potential for superior efficacy compared to HLX43 monotherapy or an anti-EGFR antibody combined with chemotherapy, thereby offering greater clinical benefit to patients with advanced solid tumours such as sqNSCLC.
The company is currently accelerating the clinical development of HLX43. To date, over 700 patients have been enrolled globally in HLX43 studies, including more than 400 patients with NSCLC (over 60%). Among them, a multi-regional phase 2 trial (HLX43-NSCLC201) is currently underway in China, the US, Australia, and Japan. Henlius has initiated over 10 clinical studies of HLX43, covering non-small cell lung cancer (NSCLC), cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal carcinoma (NPC), metastatic colorectal cancer (mCRC), gastric/gastroesophageal junction cancer (G/GEJ), pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC). Proof-of-concept (PoC) data in CC, ESCC, NPC, and HNSCC have been or will be presented at international conferences including ESMO Asia, ASCO GI, ASCO, and ESMO. Building on its intrinsic immuno-oncology (IO) activity, Henlius is exploring combination therapies, such as with the in-house anti-EGFR antibody pimurutamab and anti-PD-1 mAb serplulimab, to maximize HLX43's clinical value.
About HLX43-NSCLC302
This study is a randomized, open‑label, multi-centre, global phase 2/3 clinical study designed to evaluate the efficacy and safety of HLX43 (anti-PD‑L1 ADC) as monotherapy or in combination with HLX07 (a recombinant anti‑EGFR humanized monoclonal antibody injection) compared with docetaxel in patients with advanced or metastatic squamous non‑small cell lung cancer (NSCLC) who have failed prior therapy. The study consists of two stages. Stage 1 is an open-label, randomized, multi-centre phase 2 study, eligible subjects will be randomized in a 1:1:1 ratio to one of the following treatment arms: Group A (HLX43 monotherapy), Group B (HLX43 in combination with HLX07) or Group C (Docetaxel). Stage 2 is an open‑label, randomized, multi-centre phase 3 study. Based on the results from Stage 1, either HLX43 monotherapy or HLX43 in combination with HLX07 will be selected as the investigational group. Approximately 566 subjects will be randomized in a 1:1 ratio to Investigational group (HLX43 monotherapy or HLX43 + HLX07) or Control group (Docetaxel). The primary objective of this study is to evaluate the clinical efficacy of HLX43 monotherapy or HLX43 combined with HLX07 in the treatment of advanced squamous NSCLC after failure of first-line treatment, and the study adopts overall survival (OS) and progression‑free survival (PFS) as dual primary endpoints. Secondary objectives of this study include evaluation of safety of HLX43 monotherapy or HLX43 in combination with HLX07 vs. docetaxel, pharmacokinetic (PK) characteristics and immunogenicity of HLX43 and HLX07, and exploration of potential predictive or resistance biomarkers.
References
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3.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
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