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The company first unveiled HLX43's proof-of-concept data in esophageal squamous cell carcinoma, providing compelling new evidence for its broad anti-tumor potential.
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It has demonstrated encouraging preliminary efficacy and a favorable safety profile, with significant potential benefit in target populations. In the 3 mg/kg cohort, the ORR and DCR reached 61.5% and 100%, respectively, with a cORR of 38.5%.
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As a potential best-in-class PD-L1 ADC, its “high efficacy and low toxicity” profile establishes a clear differentiated advantage.
Shanghai, China, January 9, 2026—Shanghai Henlius Biotech, Inc. (2696.HK) today announced the first presentation of Phase II proof-of-concept (POC) data for its PD-L1 antibody-drug conjugate (ADC), HLX43, in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO GI). The study was led by Professor Jinming Yu from Shandong Cancer Hospital. The data suggest that HLX43 holds therapeutic potential in pretreated advanced ESCC, demonstrating encouraging efficacy with a manageable safety profile. Consistent clinical activity has been observed across multiple solid tumors—including non-small cell lung cancer(NSCLC), cervical cancer(CC), ESCC, and thymic carcinoma (TC)—supporting its broad anti-tumor profile and underpinning further indication expansion.
Esophageal cancer is a prevalent malignancy worldwide, with approximately 511,000 new cases and 445,000 deaths globally in 2022 [1]. China bears the highest disease burden, reporting 224,000 new cases and 188,000 deaths in 2022, accounting for nearly half of the global incidence and mortality [2]. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype, representing over 90% of cases in high-incidence regions including China [3]. While immunotherapy combined with chemotherapy significantly improving patient survival and has become the recommended first-line standard, therapeutic options are limited for those who progressed. Second-line chemotherapies such as docetaxel or irinotecan achieve an objective response rate (ORR) of only about 7%, with a median overall survival (mOS) of 5–7 months [4,5]. For patients who further progressed beyond second-line therapy, there is currently no established standard regimen globally, highlighting a substantial unmet medical need in the later-line treatment of ESCC.
This randomized, multi-center phase 2 study evaluated the efficacy and safety of HLX43 in previously treated recurrent/metastatic ESCC. Patients with histologically or cytologically confirmed recurrent/metastatic ESCC who progressed on or are intolerant to first-line chemoimmunotherapy were enrolled and randomized 1:1:1 to receive intravenous HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg once every 3 weeks. The primary endpoints were investigator-assessed objective response rate (ORR) and progression-free survival per RECIST v1.1. Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics, immunogenicity, and biomarker explorations.
As of data cutoff date Nov 25, 2025, 37 patients were randomized to and received HLX43 at 2 mg/kg (n = 12), 2.5 mg/kg (n = 12) and 3 mg/kg (n = 13) groups. Most enrolled patients had an Eastern Cooperative Oncology Group performance status score of 1 (86.5%). Patients received a median line of prior anti-tumor therapy of 2 (range, 1–4). All (100%) patients received chemotherapy and immunotherapy, 27.0% received targeted therapy, 75.7% had a PD-L1 combined positive score ≥ 1, and the median follow-up time was 3.5 months.
Among all of the 33 response-evaluable patients, promising efficacy results were observed，with an ORR of 30.3% and a DCR of 81.8%. Notably, in the 3 mg/kg group(n=13), the ORR was 61.5%( 8 partial response) and DCR was 100.0%, with a confirmed ORR (cORR) of 38.5%.In this dose group，patients with a PD-L1 CPS ≥ 1 (n=10) had an ORR of 60.0% and a DCR of 100%, compared with an ORR of 50.0% and a DCR of 100% in those with a CPS < 1 (n=2). HLX43 conferred promising efficacy regardless of PD-L1 expression. Large-scale randomized studies are required for definitive conclusion.
In terms of safety, treatment-related adverse events (TRAEs) were reported in 33 patients (89.2%,grade ≥3, 29.7%). Most common grade ≥3 TRAEs (≥5% in incidence) included anemia (13.5%), white blood cell count decreased (13.5%), lymphocyte count decreased(8.1%)，Neutrophil count decreased(8.1%) and Pneumonia(5.4%). TRAEs led to a dose reduction in 1 patient (2.7%), treatment discontinuation in 1 patient (2.7%), and death in 1 patient（2.7%）. In the 3 mg/kg dose group, where more pronounced efficacy signals were observed, the treatment demonstrated a favorable safety profile.Grade ≥3 TRAEs were reported in 5 patients (38.5%). One patient (7.7%) required a dose reduction due to TRAEs, and no patient discontinued treatment or died due to TRAEs.
In conclusion, HLX43 conferred promising efficacy, particularly at 3 mg/kg dose, along with a manageable safety profile in patients with previously treated recurrent/metastatic ESCC. Further investigation is warranted.
HLX43 is a potential best-in-class broad 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 potent anti-tumor effects and a favorable tolerability profile in 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 were released at the 2025 ASCO Annual Meeting and 2025 WCLC, demonstrating manageable safety profile and encouraging efficacy in various solid tumors especially in patients with NSCLC.
To date, Henlius has initiated about 10 clinical studies of HLX43, covering lung cancer, CC, ESCC, head and neck squamous cell carcinoma (HNSCC), nasopharyngeal carcinoma (NPC), colorectal cancer, gastric/gastroesophageal junction cancer (G/GEJ), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC), with over 500 patients enrolled globally, including more than 300 patients with NSCLC. Proof-of-concept (PoC) results in NPC and HNSCC are also expected to be released on the upcoming international academic conferences including the 2026 ASCO and ESMO. Building on its intrinsic immuno-oncology (IO) activity, Henlius is exploring combination therapies, such as with the in-house anti-EGFR antibody HLX07, to maximize HLX43's clinical value.
Guided by its commitment to address unmet medical needs, Henlius will continue to advance its core pipeline including HLX43 to deepen the differentiated therapeutic potential of our products, accelerate the delivery of greater clinical value, and ultimately deliver more breakthrough treatment options to patients worldwide.
References
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[2] Han B, Zheng R, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53.
[3] 中华肿瘤杂志(Chinese Journal of Oncology). 2019;41(1):19-28.
[4] Kojima T, Shah MA, et al. KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148.
[5] Huang J, Xu J, et al. ESCORT Study Group. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or
metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020 Jun;21(6):832-842.