WCLC 2026 | PD-L1-Targeting ADC HLX43 Achieves Confirmed ORR of Over 40% in Previously Treated TSCC, Advancing Treatment for Difficult-to-Treat Tumors

The 2026 World Conference on Lung Cancer (WCLC) is being held in Seoul, South Korea, from September 12 to 15, 2026. At the conference, results from the dose-expansion cohort of a Phase 1 clinical study evaluating HLX43, an innovative PD-L1-targeting antibody-drug conjugate (ADC) developed by Henlius, in patients with previously treated advanced thymic squamous cell carcinoma (TSCC) were presented during the Poster Tour session. The clinical data demonstrated encouraging anti-tumor activity and a favorable safety and tolerability profile of HLX43 in advanced TSCC, marking an important early clinical proof-of-concept milestone for this novel molecule and further supporting its clinical development potential and potential therapeutic window. The study is led by Professor Jie Wang of Cancer Hospital, Chinese Academy of Medical Sciences. Thymic squamous cell carcinoma (TSCC) is an extremely rare and highly aggressive thoracic malignancy associated with poor prognosis. Platinum-based chemotherapy remains the only established first-line treatment option.1 Owing to its low incidence, large-scale prospective trials evaluating effective post-platinum therapies have been challenging to conduct. Meanwhile, existing treatment options, such as single-agent immune checkpoint inhibitors (ICIs), have achieved only limited tumor control while conferring an elevated risk of severe immune-mediated toxicities. 2-3 Consequently, patients with advanced TSCC have limited treatment options following failure of standard therapy, highlighting a significant unmet medical need. HLX43 is a potential best-in-class (BIC), broad-spectrum anti-tumor ADC designed to combine immune checkpoint blockade with the cytotoxic activity of its payload. Data presented at WCLC 2026 demonstrated encouraging anti-tumor activity and a favorable safety profile in patients with advanced or metastatic TSCC who had progressed following first-line platinum-based chemotherapy, highlighting the potential of HLX43 to advance the treatment landscape for previously treated advanced TSCC. l This is an open-label, first-in-human Phase 1 clinical study evaluating the safety, tolerability, and preliminary efficacy of HLX43 in patients with solid tumors. Results from the dose-escalation phase in solid tumors and the non-small cell lung cancer (NSCLC) dose-expansion cohort were previously presented at the 2025 ASCO Annual Meeting. The results from the TSCC dose-expansion cohort are being presented for the first time at WCLC 2026. The Phase 1a portion enrolled patients with histologically or cytologically confirmed advanced solid tumors, including TSCC. Cohort 2 of Phase 1b enrolled patients with histologically or cytologically confirmed advanced TSCC who had refractory or not amenable to standard therapy. Patients received HLX43 at 2.0 mg/kg, 2.5 mg/kg, or 3.0 mg/kg once every three weeks (Q3W). The primary endpoint of the TSCC cohort was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR), overall survival (OS), safety, immunogenicity, pharmacokinetics (PK), and biomarker analyses. Given the rarity of TSCC, patients with TSCC enrolled in Phase 1a and those enrolled in Phase 1b Cohort 2 were combined with the phase 1b cohort 2 for a pooled analysis. As of the data cutoff date of June 1, 2026, a total of 34 patients had been enrolled and treated with HLX43 at doses of 2.0 mg/kg (n=11), 2.5 mg/kg (n=12), and 3.0mg/kg (n=11). The median follow-up duration was 11.1 months, 11.4 months, and 6.9 months in the 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg groups, respectively. The median number of prior lines of anti-tumor therapy was 3 (range, 1–7), and a total of 73.5% of the patients had received prior immunotherapy. Lung and liver metastases were reported in 61.8% and 35.3% of patients, respectively, indicating a heavily pretreated population with unfavorable baseline disease characteristics. Among 33 response-evaluable patients, blinded independent central review (BICR) per RECIST v1.1 demonstrated a confirmed ORR (cORR) of 45.5% and a disease control rate (DCR) of 87.9%. cORR was 58.3% and 54.5% in the 2.5 mg/kg and 3.0 mg/kg groups, respectively, while DCR was 100.0% and 90.9%, respectively. At the time of analysis, median PFS, OS, and DOR had not yet been reached. The 6-month PFS rates were 100.0% and 90.9% in the 2.5 mg/kg and 3.0 mg/kg groups, respectively. Subgroup analyses showed objective anti-tumor activity at the potential recommended Phase 2 doses (RP2Ds) of 2.5 mg/kg and 3.0 mg/kg in patients with TSCC regardless of prior immunotherapy status and across different levels of PD-L1 expression. These findings warrant further investigation in larger patient populations. In terms of safety, grade ≥3 treatment-related adverse events (TRAEs) were reported in 22 patients (64.7%). The most common grade ≥3 TRAEs were decreased lymphocyte count, decreased white blood cell count, and decreased neutrophil count. Two patients (5.9%), one each in the 2.0 mg/kg and 3.0 mg/kg groups, discontinued treatment due to TRAEs. Treatment-related serious adverse events (SAEs) occurred in five patients (14.7%), including three patients in the 2.0 mg/kg group and two in the 3.0 mg/kg group. One patient (2.9%) in the 2.0 mg/kg group experienced a grade ≥3 immune-related adverse event (irAE). No treatment-related deaths were reported. HLX43 is the first PD-L1-targeting ADC globally to advance into clinical development for thymic carcinoma. Its international multicenter clinical studies are currently underway in China, the United States, Japan and other countries. In October 2025, HLX43 received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA), underscoring its potential to address a significant unmet medical need in this rare and highly aggressive malignancy. As a potential best-in-class (BIC) broad-spectrum anti-tumor PD-L1 ADC, HLX43 has also demonstrated encouraging therapeutic potential across multiple solid tumors, including non-small cell lung cancer (NSCLC), TSCC, gynecologic cancers, and esophageal squamous cell carcinoma (ESCC). Results from its first-in-human study and proof-of-concept data across multiple solid tumors have been presented at major international oncology meetings, including ASCO and WCLC, further demonstrating its potential for robust efficacy with a favorable safety profile. In addition, Henlius is actively exploring the combination potential of HLX43 with other therapies, including the anti-EGFR monoclonal antibody pimurutamab (HLX07) and HANSIZHUANG (serplulimab, trade name in Europe: Hetronifly®). To date, the company has initiated more than ten clinical studies of HLX43 as monotherapy or in combination regimens, with over 1,500 patients enrolled globally, continuing to evaluate its broad therapeutic potential across multiple solid tumors. 参考文献 References 1. Riely, et al. J Natl Compr Canc Netw. 2025; 23(6):255-269. 2. Arunachalam, et al. Lung Cancer. 2023; 176:132-139. 3. Cho, et al. J Clin Oncol. 2019; 37(24):2162-2170.

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