- The encouraging efficacy observed across multiple solid tumors corroborates the broad-spectrum anti-tumor potential of HLX43
- Phase 2 clinical data of HLX43 in advanced cervical cancer presented in Proffered Paper Session at the 2025 ESMO Asia
- Encouraging preliminary efficacy was observed, with an ORR of 41.4% and DCR of 82.8% in the overall population, rising to 70.0% and 100% in the 3 mg/kg group, alongside a manageable safety profile
Shanghai, China, December 5, 2025—Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the results from a phase 2 proof of concept (POC) study of Henlius’ PD-L1 antibody-drug conjugate (ADC) HLX43 in recurrent/metastatic cervical cancer were first presented in Proffered Paper Session at the 2025 ESMO Asia Congress. The results demonstrated encouraging antitumor activity, providing further evidence of its broad-spectrum antitumor activity, previously observed in non-small cell lung cancer and thymic carcinoma.
Promising CC Data Add to Growing Evidence for Broad-Spectrum Potential
Cervical cancer (CC) and other gynaecological cancer pose a serious threat to women's health [1-2], particularly with poor prognosis in advanced-stage patients. Approximately 30% of advanced CC patients experience disease recurrence after first-line combination therapy [3], with a 5-year survival rate of about 17% [4]. The objective response rate (ORR) of second-line chemotherapy, including docetaxel, is only around 13.2% [5]. Although PD-1 inhibitors and the tissue factor (TF)-targeting antibody-drug conjugate (ADC) tisotumab vedotin have been approved, their efficacy in recurrent/metastatic CC after prior treatment remains limited, with ORR typically below 18% [6-9]. There is an urgent need for more effective therapeutic options with greater clinical benefits.
This open-label, randomised, multicentre phase 2 study was led by Academician Jinming Yu from the Shandong Cancer Hospital. Patients with histologically confirmed recurrent/metastatic CC who had previously failed, intolerant to, or contraindicated for standard first-line therapy were randomised 1:1:1 to receive HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg 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 measures, safety, pharmacokinetics, immunogenicity, and biomarker explorations.
By the data cutoff date of September 1, 2025, 30 patients were enrolled and randomized to receive HLX43 at 2 mg/kg (n=10), 2.5 mg/kg (n=10) and 3 mg/kg (n=10). Over 80% of the patients had a PD-L1 combined positive score ≥ 1. The median line of prior antitumor therapy was 2.0 (range, 1–4). All patients received platinum-based chemotherapy, 60% received targeted therapy, approximately 50% received immunotherapy, and the median follow-up time was 3.5 months.
Among the 29 response evaluable patients, investigator-assessed ORR was 41.4% and disease control rate (DCR) was 82.8%. ORR, and DCR for the 3 mg/kg dose group was 70.0%, and 100%, respectively. The median Progression-Free Survival (PFS) has not yet been reached.
Subgroup analysis demonstrated that HLX43 exhibited promising preliminary efficacy in PD-L1 positivive(CPS≥1) advanced cervical cancer patients, with an ORR of 45.8% and a DCR of 87.5%, respectively. Notably, a signal of efficacy was also observed in PD-L1 negative (CPS <1) patients, with one patient in the 2 mg/kg dose group achieving partial response (PR). However, as the sample size of this study was limited and the population predominantly consisted of PD-L1 positive patients (>80%), these findings are preliminary. Further investigation in larger, randomized controlled trials is required to adequately characterize the efficacy of HLX43 in the PD-L1 negative subgroup.
In terms of safety, grade ≥3 treatment-related adverse events were reported in 18 (60.0%) patients, most commonly neutrophil count decreased (30.0%), anemia(30.0%) and lymphocyte count decreased (23.3%). Dose reductions due to TRAEs were reported in 6 patients (20.0%), with no TRAE-related treatment discontinuations and TRAE-related death. Immune-related adverse events were observed in 7 (23.3%) patients, primarily including endocrine disorder and rash. No grade 3 or higher immune-related adverse events (irAEs) were reported. This finding is supportive of an immunomodulatory mechanism of action for HLX43 and indicates a manageable and favorable immune-related safety profile.
HLX43, particularly at 3 mg/kg, exhibited promising efficacy and manageable safety in patients with previously treated recurrent/metastatic CC. Further investigation of HLX43 is warranted.
Compelling Efficacy in Lung Cancer Lays Foundation for Blockbuster Profile
HLX43 is a potential best-in-class as well best-in-disease broad-spectrum anti-tumor ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Preclinical data has shown that, HLX43 has good 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, including squamous and non-squamous NSCLC patients (sqNSCLC and nsqNSCLC), patients with or without EGFR mutation, patients with or without brain metastasis, and PD-L1 positive or negative patients.
The company is currently accelerating the clinical development of HLX43. To date, over 500 patients enrolled globally for HLX43, including more than 270 patients with NSCLC. With its efficacy in later-line NSCLC being validated, Henlius plans to initiate additional Phase 3 clinical studies for HLX43 in lung cancer. These trials will encompass a second-line, head-to-head study comparing HLX43 against docetaxel, as well as explorations in first-line treatment and neoadjuvant therapy regimens. Meanwhile, as the first PD-L1 ADC developed for thymic carcinoma globally, HLX43 is advancing its international multi-center clinical trials concurrently in China, the U.S., Australia, etc. In October 2025, based on the compelling preliminary efficacy data from later-line settings in thymic carcinoma (TC), the U.S. FDA granted Orphan Drug Designation (ODD) to HLX43 for the treatment of Thymic epithelial tumors (TETs), highlighting the drug's potential to address the significant unmet need for ADC therapies in this disease.
In addition to NSCLC and TC, Henlius is actively exploring HLX43's therapeutic potential in various solid tumors. The company has initiated about 10 clinical studies for HLX43, covering CC, ESCC, head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), colorectal cancer (CRC), gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC). Proof-of-concept (PoC) results in ESCC, NPC and G/GEJ are also expected to be released on the upcoming international academic conferences including the ASCO Gastrointestinal (GI) Cancers Symposium, 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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[9] Vergote I, et al. NEJM. 2024 Jul; 391(1):44-55. ADC, antibody-drug conjugate; CC, cervical cancer; DAR, drug-antibody ratio; mPFS, median progression-free survival; ORR, objective response rate; PD-L1, programmed cell death-ligand 1; TME, tumour microenvironment; Top1, topoisomerase 1.