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The Updated Clinical Results for PD-L1 ADC HLX43 at the 2025 WCLC, Demonstrate Outstanding Efficacy in NSCLC

2025-09-07

  • Broad Therapeutic Effects: HLX43 exhibits outstanding efficacy in IO & chemo treated NSCLC. The ORR was 28.6% for ≥4L squamous NSCLC patients, 30.0% for those who previously received docetaxel; cORR was 46.7% for EGFR wild-type non-squamous NSCLC, and 60.0% for those receiving HLX43 at 2.5 mg/kg

  • Biomarker Independent: HLX43 demonstrates robust anti-tumor efficacy in various types of NSCLC (with or without EGFR mutation, with or without brain metastases, PD-L1 positive and negative). cORR was 36.4% and DCR was 100.0% for patients with brain metastasis

  • Favorable Safety Profile：Low hematological toxicity (Grade ≥3 TRAEs) was observed for HLX43, supporting its potential for expansion into first-line setting and combination regimens. The most common grade ≥3 TRAEs include anemia (19.6%), white blood cell count decreased (19.6%), and platelet count decreased (3.6%). Immune-related AE (irAE) was reported, indicating HLX43 is capable of eliciting immunotherapeutic effects


The 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (IASLC) was held from September 6-9 in Barcelona, Spain‌. Among the highlights is the updated results of the Phase 1 clinical trial of HLX43, Henlius’ PD-L1 ADC, which secured spots in both the oral presentation and poster tour session. During the Joint IASLC-CSCO-CAALC Session co-hosted by IASLC, the Chinese Society of Clinical Oncology (CSCO), and the China Lung Cancer Prevention and Treatment Alliance (CAALC), HLX43's updated phase 1 results were reported in the form of an oral presentation on September 6 (11:00 AM-11:06 AM). Professor Jie Wang from the Cancer Hospital of the Chinese Academy of Medical Sciences serves as the leading principal investigator(PI) of this study.


The updated data further validated HLX43‘s outstanding efficacy in advanced/ metastatic solid tumors such as non-small cell lung cancer (NSCLC). It is poised to offer a superior treatment option for heavily treated NSCLC patients who have failed standard therapies (including immunotherapy, chemotherapy, targeted therapy, etc.) . Furthermore, with its broad-spectrum anti-tumor profile, HLX43 may serve as a cornerstone therapeutic agent, expanding into front-line treatment and combination therapy regimens. The results from the phase 1 clinical trial of HLX43 has been first released at the 2025 ASCO Annual Meeting.


Sustained Efficacy in NSCLC, Highlights Potential for EGFR Wild-Type Later-Line Setting


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].


The updated data released at the 2025 WCLC was from the open-label, first-in-human phase 1 clinical trial evaluating the safety, pharmacokinetics, and preliminary efficacy of HLX43 (Anti-PD-L1 ADC) in patients with advanced/metastatic solid tumors (with updated NSCLC cohort data). This study includes two parts. Phase 1a and 1b were a dose escalation and dose expansion phase, respectively. In phase 1a, patients with histologically or cytologically confirmed advanced/metastatic malignant solid tumors that were refractory to or could not receive standard therapies received intravenous HLX43 at 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 2.5 mg/kg, 3 mg/kg, or 4 mg/kg, Q3W. In phase 1b, patients with advanced/metastatic non-small cell lung cancer (NSCLC) refractory to standard treatment received HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg, Q3W. The primary endpoints for phase 1b were the recommended phase 2 (RP2D) dose and objective response rate (ORR).

  • Here we present results in the NSCLC patients (from the phase 1a + phase 1b 2.0 and 2.5 mg/kg cohorts).  Median follow-up duration was 9.0 months.

  • As of the data cut-off date Jun 28, 2025, a total of 56 (29 [51.8%] had squamous type and 27 [48.2%] had non-squamous) NSCLC patients were enrolled in phase 1a and phase 1b 2.0 and 2.5 mg/kg cohorts. In squamous population, 10 (34.5%) failed docetaxel treatment while in non-squamous NSCLC, 15 (51.8%) had a EGFR wild-type status and 12 (48.2%) had EGFR mutations.

  • Among them, patients with non-squamous NSCLC were in the third-line or later setting (median prior lines of therapy: 2), while patients with squamous NSCLC were in the fourth-line or later setting (median prior lines of therapy: 3). Of all the patients, 54 (96.4%) had received platinum-based chemotherapy, 50 (89.3%) had received immunotherapy, 26 (46.4%) had received targeted therapy, and 14 (25.0%) had been treated with docetaxel.

  • Investigator-assessed ORR in the 54 response-evaluable patients was 37.0%, with a disease control rate (DCR) of 87.0%.

  • Subgroup analysis showed that in heavily pre-treated patients with squamous NSCLC (fourth-line or later, n=28), HLX43 conferred an ORR of 28.6% and a DCR of 82.1%, representing a significant clinical benefit compared to standard therapy docetaxel (ORR=12.8%). Notably, in patients who had received prior docetaxel treatment (n=10), the ORR reached 30.0% with a DCR of 80.0%. Furthermore, among these patients who receive HLX43 at the 2 mg/kg dose (n=15), ORR was 40.0% with a DCR of 73.3%, underscoring its potent therapeutic potential in heavily treated squamous NSCLC.

  • ORR was 46.2%, with a DCR of 96.2% in the third-line or later non-squamous NSCLC population (n=26). Notably, confirmed ORR (cORR) was 46.7% for patients with an EGFR wild-type non-squamous NSCLC (n=15). Among these patients, cORR was 60.0% for those receiving HLX43 at 2.5 mg/kg (n=5)，highlighting superior efficacy of HLX43 in the non-squamous NSCLC subgroup.

  • In advanced NSCLC patients with brain metastasis (n=11), HLX43 still delivered significant clinical benefits, with a cORR of 36.4% and DCR of 100.0%.

  • Moreover, HLX43 exhibits rubust efficacy in PD-L1 negative (TPS <1%, n=21) patients,  with a ORR of 38.1% and DCR of 85.7%, indicating its differented therapeutic potential to cover a broader patient population regardless of PD-L1 expression.

  • In terms of safety and tolerability, the most common grade ≥3 TRAEs were anemia (19.6%), white blood cell count decreased (19.6%), neutrophil count decreased (16.1%), and lymphocyte count decreased (12.5%). Platelet count decreased was reported in 3.6% of all treated patients. Building onto the favorable safety profile previously disclosed at the 2025 ASCO annual meeting, HLX43 continued to demonstrate low hematological toxicity, supporting its potential for expansion into first-line setting and combination therapies.

  • Immune-related AE was reported in 12 (21.4%) patients. Immune-mediated lung disease was reported in 8 (14.3%) patients, most of which were grade 1-3.

  • In these patients with immune-mediated lung disease, the cORR was 50.0% and 100% tumor shrinkage was observed, highlighting the immunotherapeutic effects of HLX43 in addition to its payload-mediated cytotoxic tumor cell killing.

Potential Best-in-class PD-L1 ADC, Advances Global Development in China, the U.S., Japan, and Australia etc. Key Markets


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 non-small cell lung cancer (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.


Currently, Henlius is advancing the clinical development of HLX43 at full speed, with over 300 patients enrolled globally and patient recruitment progressing smoothly in multiple countries including China, the U.S., and Japan. For NSCLC, HLX43 has already been approved to conduct phase 2 MRCT in China, the U.S., Japan and Australia, with first patients successfully dosed in both China and the U.S. Simultaneously, as the world's first PD-L1 ADC indicated for thymic carcinoma (TC), HLX43 has received clinical trial approvals for the indication in the U.S. and other regions. A MRCT is planned to be initiated, aiming to fill the therapeutic gap in ADC treatment for this aggressive cancer type.


In addition, the company is also accelerating the phase 2 clinical development of HLX43 in various solid tumors, including 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/gastroesophageal junction cancer (GC/GEJC). Both monotherapy and combination therapies of HLX43 with other products are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and immunotherapy-induced immune activation. 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.



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] Stanzione, B.; et al. Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor (EGFR) Common Mutations: New Strategies. Cancers 2025, 17, 1515.

[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.