June 30, 2026 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that that the first patient has been dosed in a phase 1 clinical study (HLX48-FIH101) of its independently developed c-METxEGFR bispecific antibody–drug conjugate (ADC), HLX48 for injection, in China. for the treatment of advanced and metastatic solid tumors. This open-label, dose-escalation, first-in-human phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics (PK) profiles, and preliminary efficacy of HLX48 in patients with advanced/metastatic solid tumors. Previously, HLX48 received regulatory approval to initiate clinical trials in both China and Australia in May 2026. The company will advance the phase 1 clinical development of HLX48 across both regions.
EGFR (epidermal growth factor receptor) and c-MET (mesenchymal-epithelial transition factor, encoded by the MET gene) are receptor tyrosine kinases frequently dysregulated in a variety of solid tumors. MET amplification has been recognized as a key mechanism driving acquired resistance to EGFR-targeted therapies.1 Accordingly, dual inhibition of EGFR and c-MET represents a strategic approach to overcome resistance and enhance clinical response. Despite promising preliminary clinical activity, EGFR/c-MET bispecific antibodies face limitations in response rates and disease control.2 Bispecific antibody–drug conjugates (bispecific ADCs) are designed to deliver synergistic anti-tumor effects by combining precise antibody targeting with potent cytotoxic payloads, providing a potentially more effective therapeutic option.3
HLX48 is a novel ADC candidate independently developed by Henlius based on its proprietary Hanjugator™ ADC platform. It consists of a c-METxEGFR bispecific antibody conjugated to a camptothecin-based DNA topoisomerase I inhibitor payload, with best-in-class therapeutic potential. The molecule features a highly hydrophilic linker strategy and a moderate-potency payload, with a drug-to-antibody ratio (DAR) of approximately 4, designed to achieve an optimal balance between robust anti-tumor activity and manageable toxicity. This enables maximized clinical dosing while fully leveraging the bispecific antibody’s signal-blocking and immunomodulatory functions. In addition, HLX48 is engineered with an affinity-differentiated design, exhibiting higher affinity for c-MET than EGFR, allowing preferential targeting of tumors with high c-MET expression while potentially reducing target-related toxicity associated with EGFR expression in normal tissues and thereby broadening the therapeutic window. Moreover, the optimized linker-payload design enables strong bystander killing: once internalized, the released cytotoxin can diffuse to adjacent tumor cells with low or no antigen expression, helping to overcome tumor heterogeneity and enhancing overall anti-tumor efficacy.
Preclinical pharmacological studies have demonstrated that HLX48 exhibits significant anti-tumor activity in multiple tumor models. Its conjugate exhibits bystander killing over 10-fold stronger compared with deruxtecan. In preliminary toxicology studies, HLX48 showed good tolerability in cynomolgus monkeys at 60 mg/kg administered once every three weeks (Q3W) for three doses.
HLX48 derives its differentiated design from Hanjugator™, Henlius' proprietary next-generation ADC platform. Hanjugator™ employs a highly hydrophilic camptothecin-based linker–payload system that can flexibly tune payload potency across different targets. The platform preserves antibody biological functions while synergistically enhancing anti-tumor activity and expanding the therapeutic window. It also supports multiple cytotoxic mechanisms, and differentiated payload design may help overcome common drug resistance, providing a differentiated solution for next-generation ADC development. Leveraging this platform, the Company has independently developed more than 12 next-generation ADC assets with Best-in-class or First-in-class potential, including HLX48 (c-MET x EGFR bispecific ADC), HLX49 (HER2 biparatopic ADC), HLX403 (CDH17 ADC), HLX402 (ADAM9 ADC) and HLX85 (ALPP/ALPPL2 ADC). The company continues to accelerate the advancement of additional candidates into clinical development.
Moving forward, Henlius will continue to focus on unmet clinical needs by fully leveraging its integrated platform advantages in antibody-based drugs, expanding disease areas, accelerating the development of differentiated molecules, and bringing more high-quality, affordable innovative therapies to patients worldwide.
About HLX48-FIH101
This study is an open-label, first-in-human phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetic (PK) profiles, and preliminary efficacy of HLX48 in subjects with advanced/metastatic solid tumors. The study includes six dose cohorts ranging from 1.5 mg/kg to 15 mg/kg. Eligible subjects will receive intravenous (IV) infusions of HLX48 monotherapy at specified dose levels administered once every three weeks (Q3W). Following the completion of dosing and a 21-day safety observation period for all subjects in a given cohort, the Safety Review Committee (SRC) will evaluate the data to determine whether to initiate the next dose level. The primary endpoints aim to evaluate the incidence of dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) of HLX48 monotherapy. Secondary endpoints include safety indicators such as adverse events, PK parameters, and immunogenicity, as well as efficacy indicators including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), alongside the exploration of potential predictive biomarkers.
References
1. Wang Q, et al. MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer. J Hematol Oncol. 2019;12(1):63.
2. Park K,et al. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021;39(30):3391-3402.
3. Comer F, et al. Abstract 5736: AZD9592: An EGFR-cMET bispecific antibody-drug conjugate (ADC) targeting key oncogenic drivers in non-small-cell lung cancer (NSCLC) and beyond. Cancer Research, 2023.
