HLX43 demonstrated encouraging antitumour activity in previously treated NSCLC patients regardless of histology or PD-L1 expression. This analysis included ex-China patients for the first time, with key efficacy endpoints assessed by blinded independent central review (BICR) and the first disclosure of progression-free survival (PFS) data.
In patients with EGFR wild-type nonsquamous NSCLC (nsqNSCLC), HLX43 achieved a confirmed objective response rate (cORR) of 36.8% and a median progression-free survival (mPFS) of 6.67 months. In patients with squamous NSCLC (sqNSCLC), cORR and mPFS reached 33.3% and 6.34 months, respectively. Among sqNSCLC patients previously treated with docetaxel, cORR further increased to 46.7%, with an mPFS of 6.90 months.
Based on the efficacy and manageable safety profile observed with HLX43 monotherapy, Henlius will continue to explore its potential in earlier-line treatment settings and evaluate its ability to deliver more durable clinical benefit for patients.
Shanghai, China, May 31, 2026 – Henlius (2696.HK) announced that key subgroup data from its core innovative asset, the PD-L1 antibody-drug conjugate (ADC) HLX43, in non-small cell lung cancer (NSCLC) were presented in a Rapid Oral Abstract Session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The presentation was based on a pooled analysis of NSCLC patients enrolled in the first-in-human Phase 1 study (HLX43-FIH101) and the global multicentre Phase 2 study (HLX43-NSCLC201), and included the first disclosure of long-term clinical benefit data, including progression-free survival (PFS). The results demonstrated that HLX43 monotherapy exhibited encouraging antitumour activity and a manageable safety profile in previously treated NSCLC patients. Notably, promising efficacy signals were observed in patient populations with limited treatment options, including those with EGFR wild-type nonsquamous NSCLC (nsqNSCLC) and squamous NSCLC (sqNSCLC) that had progressed following prior docetaxel treatment, providing important support for the continued clinical development of HLX43.
HLX43 is a potentially best-in-class and best-in-disease broad-spectrum antitumour ADC that combines immune checkpoint blockade with the cytotoxic activity of a topoisomerase inhibitor payload. By precisely conjugating a fully human IgG1 anti-PD-L1 antibody with an innovative linker-payload platform, HLX43 has demonstrated a favourable balance of antitumour activity and tolerability in clinical studies. At this year's ASCO Annual Meeting, data presented for HLX43 across NSCLC and nasopharyngeal carcinoma (NPC) further supported its potential as a biomarker-independent therapeutic option across multiple tumour types.
Reflecting the Challenges of Real-World Clinical Practice in Heavily Pretreated Patients
As of February 28, 2026, a total of 205 patients with advanced NSCLC had been enrolled in the study. Notably, ex-China patients were included in the analysis for the first time, further reflecting the continued advancement of HLX43’s global development programme. The study population comprised 95 patients with sqNSCLC and 110 patients with nsqNSCLC, including 63 patients with EGFR wild-type tumours and 47 patients with EGFR-mutant disease. Overall, the study population represented a heavily pretreated cohort with a substantial disease burden. Prior platinum-based chemotherapy had been administered in 99.0% of patients, while 82.0% had received prior immunotherapy, 41.0% had received targeted therapy, and 24.4% had previously been treated with docetaxel. Nearly 40% of patients had received three or more prior lines of therapy. Importantly, the vast majority of patients had undergone platinum-containing treatment regimens before receiving HLX43, reflecting prolonged treatment exposure and the cumulative toxicity and tolerability challenges commonly encountered in routine clinical practice. In addition, 27.8% of patients had bone metastases, 13.7% of patients had brain metastases and 13.7% had liver metastases, further demonstrating the complexity and disease burden of this real-world advanced NSCLC population.
Based on prior dose-escalation and dose-expansion findings, encouraging preliminary efficacy signals were observed with HLX43 at 2.0 mg/kg in patients with sqNSCLC and at 2.5 mg/kg in patients with nsqNSCLC. These dose levels were therefore selected as the recommended Phase 2/3 doses (RP2/3D) for the respective patient populations. To further evaluate the clinical benefit of HLX43 in patients with the greatest unmet need, this analysis focused on 68 key efficacy-evaluable patients treated at the RP2/3D levels and assessed by blinded independent central review (BICR), including 33 patients with sqNSCLC treated at 2.0 mg/kg and 35 patients with nsqNSCLC treated at 2.5 mg/kg. Among the nsqNSCLC cohort, 19 patients had EGFR wild-type tumors and 16 had EGFR-mutant disease, providing the basis for subsequent subgroup efficacy analyses.
Promising Activity Observed in Difficult-to-Treat Later-Line NSCLC Populations, Highlighting Broad Therapeutic Potential
Despite a heavily pretreated patient population—including patients who had failed multiple prior lines of therapy—and the use of the more stringent blinded independent central review (BICR) assessment, HLX43 continued to demonstrate encouraging antitumour activity, supporting its potential clinical value in later-line NSCLC treatment. Consistent and promising efficacy signals were observed across several clinically relevant subgroups:
Encouraging efficacy signals in EGFR wild-type nsqNSCLC: Among patients with EGFR wild-type nonsquamous NSCLC treated with HLX43 monotherapy at 2.5 mg/kg (n=19), the confirmed objective response rate (cORR) was 36.8%, the confirmed disease control rate (cDCR) was 94.7%, and the median progression-free survival (mPFS) was 6.67 months. Given the limited treatment options available for this patient population following prior immunotherapy and chemotherapy, these findings support the further development of HLX43 as a potential treatment option in EGFR wild-type nonsquamous NSCLC.
Antitumour activity maintained in sqNSCLC patients previously treated with docetaxel: In patients with sqNSCLC, cORR and mPFS reached 33.3% and 6.34 months, respectively; In patients with sqNSCLC who had previously failed docetaxel treatment and received third-line or later therapy (2.0 mg/kg, n=15), HLX43 monotherapy achieved a cORR of 46.7%, a cDCR of 80.0%, and an mPFS of 6.90 months. These results compare favourably with historically reported response rates for conventional chemotherapy in this setting and suggest that HLX43 may represent a potential treatment option for patients with heavily pretreated squamous NSCLC who have progressed following standard therapies.
Broad therapeutic potential independent of biomarker selection: Among patients with PD-L1-positive tumours (TPS ≥1%, n=29) and those with PD-L1-negative or unevaluable tumours (TPS <1% or NE, n=39), the cORRs were 37.9% and 33.3%, respectively, while the cDCRs reached 89.7% and 84.6%, respectively, with no meaningful difference observed between the two groups. Notably, the mPFS in the PD-L1-negative subgroup remained 5.49 months. These findings suggest that HLX43 may provide clinical benefit regardless of PD-L1 expression status, supporting its potential as a broadly applicable therapeutic approach and further expanding its potential utility across difficult-to-treat patient populations.
Manageable Monotherapy Safety Profile Supports Exploration in Earlier-Line Settings
As of February 28, 2026, a pooled analysis of 205 patients with NSCLC demonstrated that HLX43 exhibited an overall manageable safety profile. Treatment-related adverse events (TRAEs) were predominantly Grade 1–2, and no new safety signals were identified. Overall, 97.1% of patients experienced TRAEs, with Grade ≥3 TRAEs reported in 48.8% of patients. The most common Grade ≥3 TRAEs were decreased lymphocyte count (27.3%), anemia (14.1%), decreased white blood cell count (13.7%), and decreased neutrophil count (11.2%). The vast majority of adverse events were clinically manageable. Rates of TRAEs leading to treatment interruption, dose reduction, and treatment discontinuation were 38.0%, 12.2%, and 7.8%, respectively, while TRAEs leading to death occurred in 1.0% of patients.
Notably, across the 205-patient analysis population encompassing multiple dose levels, NSCLC subtypes, and treatment backgrounds, HLX43 demonstrated a consistent and manageable safety profile. While combination regimens remain the cornerstone of first-line NSCLC treatment, the ability of a therapeutic candidate to maintain favorable tolerability while delivering meaningful efficacy is a critical prerequisite for advancement into earlier treatment settings. As a PD-L1-targeting ADC, HLX43 combines targeted delivery with antitumour activity through a mechanism distinct from conventional immunotherapy-plus-chemotherapy approaches. The encouraging efficacy signals and manageable safety profile observed with HLX43 monotherapy in this study support further exploration of earlier-line treatment strategies, with the potential to optimize the patient treatment experience while maintaining efficacy and enabling more durable clinical benefit.
Accelerating Global Clinical Development and Unlocking the Full Potential of HLX43
As a cornerstone of Henlius' global development strategy for HLX43, the HLX43-NSCLC201 study is currently advancing across multiple countries and regions, including China, Europe, the United States, Japan, and Australia. Building on this foundation, Henlius continues to accelerate the global clinical development of HLX43. To date, approximately 1000 patients have been enrolled globally across HLX43 clinical studies, with NSCLC accounting for over 60% of the total enrollment (more than 500 patients). Beyond NSCLC, Henlius has initiated more than ten clinical studies evaluating HLX43 as monotherapy or in combination with other therapies across a broad range of solid tumours, including cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal carcinoma (NPC), metastatic colorectal cancer (mCRC), gastric/gastroesophageal junction (G/GEJ) cancer, pancreatic ductal adenocarcinoma (PDAC), and breast cancer (BC). Henlius continues to explore the therapeutic potential of HLX43 across multiple tumour types, with proof-of-concept data in CC, ESCC, NPC, and HNSCC having been presented or scheduled for presentation at major international congresses, including ESMO Asia, ASCO GI, ASCO, and ESMO. In addition to monotherapy development, Henlius is actively investigating combination strategies based on the immuno-oncology activity observed with HLX43. These include combinations with the Henlius’ proprietary anti-EGFR monoclonal antibody pimurutamab (HLX07) and anti-PD-1 monoclonal antibody serplulimab (trade name: Hetronifly® in Europe), among other therapeutic approaches. These efforts aim to further evaluate the potential of HLX43 in earlier-line treatment settings and across diverse combination strategies.
Looking ahead, Henlius will continue to advance the clinical development of HLX43 and other core innovative assets in lung cancer and multiple solid tumours. As additional efficacy, survival, and safety data become available, Henlius aims to further define the clinical positioning of HLX43 across different NSCLC subtypes, lines of therapy, and treatment combinations, with the goal of expanding treatment options for patients with advanced NSCLC who currently face limited therapeutic choices.
About HLX43-FIH101
This open-label, first-in-human Phase 1 study conducted in China was designed to evaluate the safety, pharmacokinetics (PK), and preliminary antitumor activity of HLX43 in patients with advanced or metastatic solid tumours. The study investigated dose levels ranging from 0.5 mg/kg to 4.0 mg/kg to determine the maximum tolerated dose (MTD), and further evaluated the efficacy of HLX43 at doses of 2.0–3.0 mg/kg in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who had progressed on or were refractory to standard therapies, with the aim of identifying the recommended Phase 2 dose (RP2D).
About HLX43-NSCLC201
This study is an open-label, international, multi-centre Phase 2 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-centre Phase 2 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.