On August 13, 2025 (Pacific Time), the World Conference on Lung Cancer (WCLC) 2025 has officially unveiled the list of accepted abstracts. Ten studies on Henlius' innovative PD-L1 ADC HLX43, anti-EGFR mAb HLX07 and anti–PD-1 monoclonal antibody(mAb) HANSIZHUANG (serplulimab) have been selected for multiple sessions, including oral presentations, poster tours, and poster presentations. Among these, 4 will be featured as oral presentations and 2 as poster tours. The selected studies span first-line treatment for non-squamous non–small cell lung cancer (nsNSCLC), squamous non–small cell lung cancer (sqNSCLC), and extensive-stage small cell lung cancer (ES-SCLC). In addition, innovative therapies are being actively promoted to explore the therapeutic potential of immunotherapy in a wide range of populations, including the perioperative setting for patients with NSCLC and patients with brain metastases.

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]. Lung cancer is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC making up approximately 85% of all cases. NSCLC can be further divided into sqNSCLC(about 30%), nsNSCLC(about 50%), and other subtypes.

1.Release of the Updated Abstract for Henlius’PD-L1 ADC HLX43 at 2025 WCLC

On August 13, 2025, Pacific Time, the official website of the 2025 World Conference on Lung Cancer (WCLC) released the selected research abstracts for this year’s conference.Among the highlights is the updated abstract for the first-in-human Phase 1 clinical trial of HLX43, Henlius’ PD-L1 ADC. The full set of updated data will be presented in poster tour session at the WCLC by Professor Jie Wang from Cancer Hospital Chinese Academyof Medical Sciences, the Leading Principal investigator (PI) of this study, on September 8, 2025, from 2:31 to 2:39 PM in Spain.

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-tumour effects and a favorable tolerability profile in non-small cell lung cancer (NSCLC), cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumour 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.

According to the updated abstract, HLX43 continues to demonstrate a high response rate in patients with advanced solid tumors, particularly in pretreated NSCLC patients who failed checkpoint inhibitor therapy. HLX43 exhibits superior efficacy in specific subgroups, with an objective response rate (ORR) of 47.4% in EGFR wild-type non-squamous NSCLC, while maintaining a favorable safety profile. Notably, HLX43 demonstrates robust efficacy regardless of PD-L1 expression, indicating its biomarker-independent antitumor potential.

· Effective in Later-Line Treatment of CPI-Resistant NSCLC：As of February 28, 2025, a total of 85 patients received HLX43. In Phase Ia (dose-escalation), 21 patients with advanced solid tumors were enrolled, while in Phase Ib (dose-expansion), 64 NSCLC patients were recruited across three cohorts (2, 2.5, and 3 mg/kg). Notably, 88.2% (75/85) of patients failed prior checkpoint inhibitor (CPI) therapy.

· Promising Efficacy in NSCLC with Notable Results in Specific Subgroups: Among the 76 NSCLC patients (69 efficacy-evaluable), ORR was 31.9% (22/69), with a disease control rate (DCR) of 87.0% (60/69). Subgroup analyses demonstrated promising efficacy of HLX43 in specific populations: the 2 mg/kg and 2.5 mg/kg cohorts in Phase Ib achieved ORRs of 38.1% (8/21) and 33.3% (7/21), respectively; CPI-refractory NSCLC patients (n=61) showed an ORR of 32.8% (20/61); EGFR wild-type non-squamous NSCLC patients (n=19) had an ORR of 47.4% (9/19).

· Favorable Safety Profile, High Efficacy with Low Toxicity: In Phase Ia, one DLT event involving febrile neutropenia was observed in the 4 mg/kg group. Treatment-related adverse events (TRAEs) were reported in 95.2% of patients, mostly Grade 1-2. Grade ≥3 TRAEs occurred in 5 patients (23.8%), all from the 3 and 4 mg/kg cohorts, most frequently decreased neutrophil count (19%), decreased white blood cell count (19.0%) and anemia (14.3%). Immune-related adverse events (irAEs) reported in this study suggests HLX43 is capable of eliciting immunotherapeutic effects. Notably, patients who reported irAEs demonstrated a higher objective response rate (ORR).

· Effective in different biomarker status: PD-L1-positive NSCLC patients (n=50) exhibited an ORR of 32.0% (16/50) while PD-L1-negative/unknown patients (n=19) achieved an ORR of 31.6% (6/19), with no significant difference observed.

In conclusion, HLX43 has demonstrated promising antitumor activity along with a manageable safety profile in patients with advanced NSCLC who were refractory to standard therapies, including those who had progressed after treatment with PD-(L)1 inhibitors. Its high efficacy with low toxicity traits support its potential in the first-line settings. Enrollment in the Phase Ib expansion cohort is ongoing. We anticipate the ongoing validation of HLX43's efficacy and safety across multiple studies, which could provide a superior treatment option for patients with advanced, refractory solid tumors, including those with non-small cell lung cancer.

2.Spotlight Oral Presentation: Demonstrating Efficacy in NSCLC

In NSCLC,at this year’s WCLC, the Phase III ASTRUM-002 study, led by Professor Yuankai Shi of the Cancer Hospital, Chinese Academy of Medical Sciences, will debut its results in an oral presentation. The study evaluates serplulimab plus chemotherapy as a first-line treatment for advanced nsNSCLC, showing a median progression-free survival (mPFS) of 11.0 months, an improvement of 5.4 months compared to chemotherapy alone, as well as clear benefit in patients with brain metastases.

Additionally, multiple investigator-initiated trials (IITs) exploring serplulimab in combination immunotherapy have been selected for Mini Oral presentations, poster tours, and poster presentations. These studies further validate the efficacy and safety of serplulimab in nsNSCLC patients with brain metastases, in EGFR-TKI–resistant cases, and in the perioperative setting for non-small cell lung cancer, underscoring its potential in broader patient populations.

The ASTRUM-002 study is a randomized, double-blind, multicentre phase 3 clinical study. Patients with locally advanced or metastatic nsNSCLC without EGFR sensitizing mutations or ALK/ROS rearrangements and no prior systemic therapy were randomized 1:1:1 to receive serplulimab + HLX04 + chemo, serplulimab +chemo, or chemo. The results indicated that serplulimab + chemo versus chemo as first-line treatment of advanced nsNSCLC significantly prolonged mPFS(11.0 months vs. 5.6 months; stratified HR= 0.55, 95% CI: 0.43-0.69, P < 0.0001), meeting the prespecified superiority criteria, with good safety profile and no new safety signals were observed. In the subgroup of patients with brain metastases, the median PFS in the serplulimab + chemo group reached 8.1 months, an extension of 4.0 months compared with the chemo group, reducing the risk of disease progression or death by 49% (HR = 0.51, 95% CI: 0.30-0.87, P = 0.0115).

Title: ASTRUM-002: First-Line Serplulimab Plus Chemotherapy With or Without HLX04 in Advanced Nonsquamous Non-small Cell Lung Cancer

Form: Oral

Session: OA05-lmmunotherapy for Special Populations

Abstract Number: 1454

Leading PI: Yuankai Shi, Cancer Hospital Chinese Academy of Medical Sciences

Time: Sunday Sep 7, 2025 4:47 PM-4:57 PM (CEST)

A Phase 2 trial evaluated serplulimab plus bevacizumab and chemotherapy in treatment-naïve non-squamous NSCLC with brain metastases. The study enrolled 40 nsNSCLC patients with untreated brain metastases to receive first line treatment of serplulimab combined with bevacizumab, pemetrexed, and carboplatin. The median sPFS was 13.3 months. The intracranial ORR was 84.6%, with a 64.1% extracranial ORR, demonstrating potent antitumor activity. Serplulimab plus bevacizumab and chemotherapy demonstrated promising intracerebral antitumor efficacy and a manageable safety profile for patients with non-squamous NSCLC with BMs in the first-line setting.

Title: Phase II Trial of Serplulimab Plus Bevacizumab and Chemotherapy for Treatment-Naive Non-Squamous NSCLC with Brain Metastases(SUPER BRAIN)

Form: Mini Oral

Session: MA10-Longer Follow Up and New IO Combinations

Abstract Number: 2266

Leading PI: Likun Chen, Sun Yat-Sen University Cancer Center

Time: Sep 9,2025 1:02 PM-1:07 PM (CEST)

3.Potential Advantageous Therapy Option for EGFR High-Expression Lung Cancer

In patients with NSCLC worldwide, the prevalence of EGFR overexpression is estimated at approximately 40%–89% (depending on histological subtype, ethnicity, and other factors), representing millions of newly diagnosed patients each year ^[2–4]. Notably, up to 89% of patients with sqNSCLC present with EGFR overexpression ^[2–3]. Henlius is actively advancing a phase 2 clinical study of HLX07, a novel anti-EGFR mAb developed by Henlius, in combination with serplulimab for the first-line treatment of EGFR high expression sqNSCLC, aiming to address the significant unmet clinical need in this population. Updated data from this study have been accepted for poster presentation at this year’s World Conference on Lung Cancer (WCLC).

This randomized, multicenter phase 2 study consisted of 4 parts and assessed different combinations of HLX07 (at various doses), serplulimab, and chemotherapy. Part 3 explored the preliminary efficacy of the tri-combination regimen in systemic treatment-naïve patients with EGFR overexpression (H-score ≥150), who were enrolled and randomly assigned to group A (n=13) and group B (n=14). Two groups of patients received intravenous HLX07 at 800 mg (group A) or 1000 mg (group B), in combination with serplulimab (300mg) and chemotherapy.

With a median follow-up of 18.6 months, both dose groups achieved an IRRC-assessed confirmed objective response rate (ORR) of around 70%, while the median overall survival (mOS) and median duration of response (mDOR) were not reached, indicating durable responses with the potential for further improvement, alongside a manageable safety profile. Notably, the group B achieved a disease control rate (DCR) of 100% and a median progression-free survival (PFS) of 17.4 months (95% CI 8.1-NE). These results demonstrate encouraging preliminary efficacy  with a manageable safety profile of HLX07 plus serplulimab and chemotherapy as first-line treatment in patients with advanced sqNSCLC, supporting further investigation of this regimen.

Title: First-line HLX07 plus serplulimab with or without chemotherapy in squamous non-small cell lung cancer: a phase 2 study

Form: Poster

Session: P3.12-Metastatic Non-small Cell Lung Cancer - Targeted Therapy

Abstract Number: 1467

Leading PI: Yilong Wu, Guangdong Provincial People's Hospital

Time: Sep 9, 2025 10:00 AM-11:30 AM (CEST)

4.Full coverage of first-line lung cancer treatment, broad benefits in ES-SCLC

Henlius continues to expand the layout of serplulimab in the field of lung cancer, achieving full coverage of first-line lung cancer treatment. In small cell lung cancer (SCLC), based on the international multicenter Phase III ASTRUM-005 study, serplulimab has been approved in nearly 40 countries and regions worldwide, including China, the UK, Germany, Singapore, and India, for the first-line treatment of ES-SCLC. The final analysis of this study was released at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showing a 4-year OS rate of 21.9%.

For ES-SCLC, the latest results from the largest real-world study in China in this field (ASTRUM-005R) were released at the 2025 European Lung Cancer Congress (ELCC). The study showed a median rwPFS of 8.2 months and a median OS of 17.2 months, providing robust evidence to support serplulimab plus chemotherapy as a first-line treatment for ES-SCLC. At this year’s WCLC, subgroup analysis data from this study in ES-SCLC patients with a PS score ≥2, as well as results from a meta-analysis in ES-SCLC patients with ECOG PS ≥2, will be presented, demonstrating the broad benefits of immunotherapy combinations for ES-SCLC patients.

Henlius continues to accelerate the global development of serplulimab for ES-SCLC, with the first patient dosed in the Janpanese bridging study. In additon, the company is conducting a phase 3 international multi-centre clinical trial of HANSIZHUANG combined with chemotherapy and radiotherapy for limited-stage SCLC (LS-SCLC).

For more research on data integrity and highlights, please stay tuned for WCLC 2025!

References:

[1]Prabhakar CN. Epidermal growth factor receptor in non-small cell lung cancer. Transl Lung Cancer Res. 2015;4(2):110-118. doi:10.3978/j.issn.2218-6751.2015.01.01

[2]Karlsen E-A, Kahler S, Tefay J, Joseph SR, Simpson F. Epidermal Growth Factor Receptor Expression and Resistance Patterns to Targeted Therapy in Non-Small Cell Lung Cancer: A Review. Cells. 2021; 10(5):1206. https://doi.org/10.3390/cells10051206

[3]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.