The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting will be held in Chicago from May 29 to June 2. At this year's ASCO Annual Meeting, the complete data on Henlius’ PD-L1 ADC, HLX43, in the treatment of non-small cell lung cancer (NSCLC) will be officially presented as a Rapid Oral Presentation on May 30, from 1:15 PM to 1:21 PM (US Central Time). Notably, this presentation will mark the first disclosure of subgroup progression-free survival (PFS) data, further validating the clinical application potential and value of HLX43 in the treatment of refractory NSCLC.
HLX43 is a novel antibody-drug conjugate (ADC) targeting programmed death-ligand 1 (PD-L1). It consists of a fully human anti-PD-L1 IgG1 antibody conjugated to a novel topoisomerase inhibitor payload via an innovative linker, with a drug-to-antibody ratio (DAR) of approximately 8. HLX43 possesses dual functions of precise toxin-mediated killing and tumour immunity. The payload can be released upon internalization into tumour cells following target binding; furthermore, the released payload can enter neighbouring tumour cells through the "bystander effect," blocking DNA replication and inducing tumour cell apoptosis. In addition, the PD-L1-targeting antibody component of HLX43 can activate immune regulatory mechanisms, exerting synergistic anti-tumour effects.
Data from the first-in-human (FIH) study and multiple proof-of-concept (PoC) studies for various solid tumours have been presented at several international academic conferences, demonstrating significant "high-efficacy, low-toxicity" therapeutic results. Notably, in the NSCLC population, HLX43 has demonstrated a clinical advantage that is independent of biomarker screening, showing potential to cover all patient subtypes. Currently, international multi-centre clinical studies for NSCLC are accelerating across China, Europe, the United States, Australia, and Japan. A Phase 2/3 international multi-centre clinical study (HLX43-NSCLC302) for advanced squamous NSCLC is set to be conducted in multiple countries including China, the US, and Japan, with the Phase 3 stage expected to be the first pivotal registrational study for HLX43 in the NSCLC field. Beyond NSCLC, HLX43 has also shown positive efficacy signals in multiple solid tumours, including gynaecological cancers and esophageal squamous cell carcinoma (ESCC). In addition to monotherapy, the company is actively exploring its combination therapy potential with innovative products such as the anti-EGFR mAb pimurutamab and the anti-PD-1 mAb serplulimab (trade name: Hetronifly® in Europe).
The NSCLC data presented at this ASCO Annual Meeting is derived from the pooled analysis of NSCLC patients in the HLX43 first-in-human Phase 1 study (HLX43-FIH101) and the global Phase 2 study (HLX43-NSCLC201), with efficacy evaluated by a Blinded Independent Central Review (BICR) committee.
The abstract for this study was officially released at 5:00 PM (US Eastern Time) on May 21:
Title:
Efficacy and Safety of HLX43 (Anti-PD-L1 ADC) in Patients with Advanced Non-small Cell Lung Cancer
Trial Design:
The phase 1 study included a dose‑escalation phase in patients with advanced solid tumours (0.5–4.0 mg/kg Q3W), followed by a dose‑expansion phase in patients with advanced or metastatic NSCLC at doses of 2.0, 2.5, and 3.0 mg/kg Q3W. The phase 2 study was conducted in NSCLC and comprised two parts: Part A was dose‑exploration for patients who had failed prior first‑line therapy and had no actionable genomic alterations, to receive HLX43 at 2.0 or 2.5 mg/kg Q3W; Part B was dose‑expansion in which patients received HLX43 at the recommended dose determined from Part A. This analysis integrated data from heavily pretreated NSCLC patients enrolled across both studies. Efficacy and safety outcomes were evaluated in the pooled population.
Results:
As of December 31, 2025, 205 patients were enrolled and received HLX43 at 1 mg/kg (n=3), 2 mg/kg (n=89), 2.5 mg/kg (n=85), 3 mg/kg (n=23), and 4 mg/kg (n=5). Patients received a median of 2 lines of prior antitumor therapy (range, 1–9). 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%. In the 2.0 mg/kg group, investigator-assessed ORR was 36.4% for squamous NSCLC (n=33); among these patients, ORR was 40.0% for those who previously failed docetaxel (n=15). ORR was 47.4%, and 50.0% for patients with EGFR-wildtype (n=19), and EGFR-mutant non squamous (n=16) NSCLC receiving HLX43 at 2.5 mg/kg. 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.
Conclusion:
HLX43 exhibited promising efficacy in patients with heavily pretreated advanced NSCLC, regardless of histology subtypes, brain metastasis and PD-L1 expression, along with manageable tolerability. Further investigation is warranted.
The data above represent the preliminary analysis results published in the ASCO abstract. With the deepening of clinical research, HLX43 has demonstrated robust anti-tumour activity and controllable safety characteristics in heavily pretreated NSCLC patients, laying the foundation for its clinical potential as a next-generation PD-L1 ADC. More in-depth subgroup efficacy evaluations, long-term survival benefit data (including key indicators such as PFS), and a more comprehensive clinical analysis from this study will be detailed during the Rapid Oral Presentation on the afternoon of May 30 (US Central Time). Please stay tuned.
In addition, phase 2 study data for HLX43 in the treatment of nasopharyngeal carcinoma (NPC) will also be presented as a poster at this ASCO Annual Meeting on May 30, from 1:30 PM to 4:30 PM (US Central Time), with the abstract officially released at 5:00 PM (US Eastern Time) on May 21:
Title:
Efficacy and safety of HLX43 (an anti-PD-L1 ADC) in previously treated recurrent/metastatic nasopharyngeal carcinoma: a multicenter, randomized phase 2 study.
Trial Design:
This randomized, multicentre trial enrolled patients with histologically or cytologically confirmed r/m NPC who had received at least second-line chemotherapy (including one prior line of platinum-based chemotherapy) and progressed on or were intolerant to programmed death (ligand) 1 (PD-[L]1) inhibitor. Patients were randomized 1:1:1 to receive 2 mg/kg, 2.5 mg/kg, or 3 mg/kg of intravenous HLX43 every 3 weeks. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) per investigator's assessments.
Results:
As of September 18, 2025, 30 patients were randomized to the 2, 2.5, or 3 mg/kg group (n = 10 for each group). The median follow-up duration was 2.8 months(range 2.1–5.6). Twenty-six patients (86.7%) had performance status 1; 27 (90.0%) had prior radiotherapy. The median line of prior systemic therapy was 3 (range 2–8). ORR was 36.7%, with partial responses (PRs) in 11 patients. ORR in the three dose groups was 20.0%, 20.0% and 70.0% (all confirmed by December 2025), respectively; disease control rate (DCR) was 50.0%, 50.0% and 80.0%. PFS data were immature. Overall, treatment-emergent adverse events (TEAEs) occurred in 29 patients (96.7%; grade ≥3,50.0%). TEAE incidence was 90.0%, 100% and 100% in the three dose groups, respectively. TEAE leading to dose reduction was reported in 3 patients (30.0%) in the 3 mg/kg group only. TEAE leading to treatment discontinuation occurred in 1 (10.0%) each in the 2.5 mg/kg and 3 mg/kg groups. There was no death due to TEAE. The efficacy and safety findings are detailed in Table 1.
Table 1. Efficacy and Safety
2.0 mg/kg | 2.5 mg/kg | 3.0 mg/kg | Total | |
PR | 2 (20.0) | 2 (20.0) | 7 (70.0) | 11 (36.7) |
SD | 3 (30.0) | 3 (30.0) | 1 (10.0) | 7 (23.3) |
PD/NE | 5 (50.0) | 5 (50.0) | 2 (20.0) | 12 (40.0) |
ORR, 95% CI（%） | 20 | 20 | 70 | 36.7 |
DCR, 95% CI（%） | 50 | 50 | 80 | 60 |
TEAEs | 9 (90.0) | 10 (100) | 10 (100) | 29 (96.7) |
Grade ≥3 TEAEs | 2 (20.0) | 7 (70.0) | 6 (60.0) | 15 (50.0) |
TEAE leading to dose reduction | 0 | 0 | 3 (30.0) | 3 (10.0) |
TEAE leading to treatment discontinuation | 0 | 1 (10.0) | 1 (10.0) | 2 (6.7) |
*NE, not evaluable. PD, progressive disease. SD, stable disease.
Conclusion:
HLX43 showed promising efficacy with a manageable safety profile in r/m NPCpatients who had progressed after second-line or later chemotherapy and PD-(L)1 inhibitors. Further investigation is warranted.
About HLX43-FIH101
This study is an open-label, dose-escalation, first-in-human Phase I clinical trial evaluating the safety and tolerability of HLX43 in patients with advanced/metastatic solid tumors. The study employs a "3+3" design with six dose levels (0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 6 mg/kg, and 8 mg/kg), with patients receiving HLX43 via intravenous infusion every three weeks. The dose-limiting toxicity (DLT) observation period is three weeks following the first dose of HLX43. The primary endpoints of the study are the proportion of patients experiencing DLT events within the DLT observation period for each dose group, and the maximum tolerated dose (MTD) of HLX43. Secondary endpoints include safety, pharmacokinetic parameters, immunogenicity, preliminary efficacy, pharmacodynamic markers, and potential predictive and resistance biomarkers.
About HLX43-NSCLC201
This study is an open-label, international, multi-center Phase II clinical trial aimed at evaluating the efficacy and safety of HLX43 in patients with advanced non-small cell lung cancer (NSCLC). The study consists of two phases: the first phase involves dose exploration to select the appropriate HLX43 dose for the second phase. The second phase is a single-arm, multi-center Phase II clinical study. The primary objective of the study is to evaluate the clinical efficacy of HLX43 in advanced NSCLC. Secondary objectives include safety, tolerability, pharmacokinetic characteristics, immunogenicity, and the exploration of potential predictive or resistance biomarkers. The primary endpoint is the objective response rate (ORR) assessed by a Blinded Independent Central Review (BICR) committee according to RECIST v1.1 criteria.
