Shanghai Henlius Biotech has announced that the first patient in the European Union has been dosed in Spain in the international multicenter Phase 2 trial HLX43-NSCLC201, evaluating HLX43, a PD-L1-targeting antibody-drug conjugate, in patients with advanced non-small cell lung cancer.
The milestone expands the global development footprint of HLX43 across major markets, with the Phase 2 study now initiated across China, the European Union, the United States, Japan, and Australia. According to Henlius, updated clinical data for HLX43 in NSCLC are expected to be presented in an oral session at the 2026 ASCO Annual Meeting (Henlius, 2026).
Why HLX43 Matters in NSCLC
Non-small cell lung cancer remains the most common form of lung cancer, accounting for approximately 85% of all lung cancer cases. Many patients are diagnosed at advanced stages, where the need for effective systemic therapies remains substantial. EGFR wild-type NSCLC represents a large subgroup, including most squamous NSCLC cases and a substantial proportion of adenocarcinomas (Chan & Hughes, 2015).
Second-line and later treatment remains an area of unmet need, particularly for patients whose disease progresses after standard therapy. Docetaxel-based chemotherapy continues to be used in many settings, but efficacy remains limited. This has created strong interest in antibody-drug conjugates that can combine targeted delivery with potent cytotoxic activity (Henlius, 2026).
What Is HLX43?
HLX43 is an investigational PD-L1-targeting antibody-drug conjugate. It is composed of a fully humanized anti-PD-L1 IgG1 antibody, a tripeptide linker, and a topoisomerase inhibitor payload, with a drug-to-antibody ratio of approximately 8.
The design is intended to combine two antitumor mechanisms. First, HLX43 binds to PD-L1-expressing tumor cells and delivers a cytotoxic payload through receptor-mediated internalization and linker cleavage. Second, the released payload may diffuse into neighboring tumor cells through a bystander effect. The antibody component may also contribute immune checkpoint modulation through PD-L1/PD-1 blockade (Henlius, 2026).
Phase 2 Study Design
HLX43-NSCLC201 is an open-label, multicenter, international Phase 2 study evaluating HLX43 in patients with advanced NSCLC.
The trial includes two parts. Part 1 focuses on dose exploration to identify the optimal dose for continued evaluation. Part 2 is a single-arm multicenter Phase 2 trial. The primary objective is to evaluate clinical efficacy, with objective response rate by blinded independent central review according to RECIST v1.1 as the primary endpoint.
Henlius reported that earlier clinical data supported 2.0 mg/kg or 2.5 mg/kg as the recommended Phase 2/3 dose range for HLX43 in NSCLC (Henlius, 2026).
Prior Clinical Signal
According to Henlius, Phase 1 data first presented at the 2025 ASCO Annual Meeting showed a manageable safety profile and encouraging activity across solid tumors, particularly in NSCLC. The company reported activity across NSCLC subgroups, including squamous and non-squamous histologies, patients with or without EGFR mutations, patients with or without brain or liver metastases, and patients with PD-L1-positive or PD-L1-negative tumors (Henlius, 2026).
These findings remain early and require confirmation in later-phase trials, but the broad activity reported across clinically distinct NSCLC populations supports continued development.
Next Development Steps
Henlius is also preparing an international Phase 2/3 study, HLX43-NSCLC302, in advanced squamous NSCLC. The Phase 3 portion is intended to become the first pivotal registrational trial for HLX43 in NSCLC.
Beyond lung cancer, Henlius is exploring HLX43 across multiple solid tumors, including esophageal squamous cell carcinoma, cervical cancer, breast cancer, gastric or gastroesophageal junction cancer, and head and neck squamous cell carcinoma. Combination studies are also ongoing to evaluate whether HLX43 can be paired with other agents to improve antitumor activity (Henlius, 2026).
Clinical Meaning
The EU first-patient dosing marks an important operational step for HLX43’s global development. For NSCLC, the key questions now are whether the encouraging early activity can be reproduced in larger cohorts, whether benefit is consistent across PD-L1 expression levels and histologic subtypes, and whether safety remains manageable at the selected Phase 2/3 doses.
If later trials confirm meaningful activity, HLX43 could represent a new ADC-based approach for patients with advanced NSCLC, especially in treatment settings where current options remain limited.