Regulatory & Policy

Henlius Bio readies first-in-class EGFR/c-MET bispecific ADC for Phase I in China

Shanghai Henlius Biotech (HKEX: 2696) announced on May 21, 2026 that China's National Medical Products Administration has approved the investigational new...

Edited by Robert McTiernan··4 min read

Shanghai Henlius Biotech (HKEX: 2696) announced approval in China for an investigational new drug application enabling a Phase I clinical trial of HLX48, a bispecific antibody-drug conjugate targeting both EGFR and c-MET. The drug will initially be assessed as a treatment for unspecified advanced and metastatic solid tumors. The IND approval marks the first-in-human entry of a molecule the company describes as the only bispecific ADC with this dual-target configuration globally.

The NMPA clearance authorizes Henlius to proceed with a Phase I dose-escalation study of HLX48 in patients with advanced or metastatic solid tumors. The trial, registered as NCT07473726, was listed as not yet recruiting as of the most recent registry update. Separately, in May 2026, the same Phase I program received acknowledgment from Australia's Therapeutic Goods Administration under that country's Clinical Trial Notification scheme, indicating Henlius is pursuing parallel first-in-human initiation across two jurisdictions.

The trial is designed as a tumor-agnostic Phase I study, enrolling patients across solid tumor types rather than restricting enrollment to a single histology. This design reflects the biological rationale for HLX48: EGFR and c-MET are co-overexpressed across a broad range of cancers, including non-small cell lung cancer, head and neck squamous cell carcinoma, gastric cancer, hepatocellular carcinoma, and colorectal cancer, among others. A histology-agnostic entry strategy allows Henlius to map efficacy signals across tumor types before narrowing development to specific indications in later phases.

EGFR and c-MET co-targeting

The HLX48 antibody-drug conjugate is designed to engage both EGFR and c-MET simultaneously on the surface of tumor cells. Upon binding, the construct induces receptor-mediated endocytosis, internalizing the antibody-payload complex into the tumor cell, where the cytotoxic payload is released intracellularly, causing DNA damage and cell death. The molecule also carries a bystander effect, meaning the released payload can diffuse to and kill adjacent tumor cells that may not express the target receptors at sufficient density, a property that may be relevant in tumors with heterogeneous antigen expression.

Beyond the ADC killing mechanism, the variable regions of the HLX48 antibody block the binding of epidermal growth factor and hepatocyte growth factor to their respective receptors, EGFR and c-MET, thereby inhibiting downstream signaling cascades that drive tumor proliferation and survival. The Fc region of the antibody additionally enables antibody-dependent cell-mediated cytotoxicity, recruiting immune effector cells to the tumor site. The result is a molecule designed to operate through at least three distinct anti-tumor mechanisms: direct cytotoxic payload delivery, receptor signaling blockade at two nodes, and immune-mediated tumor killing.

Preclinical studies, according to Henlius, demonstrated anti-tumor efficacy and a safety profile the company characterized as favorable, though no preclinical data were disclosed in the announcement. The NMPA's clearance of the IND application indicates that the regulatory package, including preclinical toxicology and pharmacology data, was sufficient to support human testing.

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Competitive context

The EGFR c-MET targeting cancer space already has one approved bispecific agent: Janssen's amivantamab (Rybrevant), a bispecific EGFR-by-MET antibody approved by the US FDA in 2021 for NSCLC with EGFR exon 20 insertion mutations, and expanded in 2024 to first-line EGFR-mutant NSCLC in combination with lazertinib.

The broader EGFR inhibitor landscape is crowded. AstraZeneca's osimertinib (Tagrisso), a third-generation EGFR tyrosine kinase inhibitor, is the standard of care for first-line EGFR-mutant NSCLC. However, MET amplification is one of the primary resistance mechanisms that drives disease progression on osimertinib, and no approved agent simultaneously addresses both EGFR and MET signaling with a cytotoxic payload in the post-osimertinib setting. Approved MET inhibitors — Novartis's capmatinib (Tabrecta) and EMD Serono's tepotinib (Tepmetko) — address MET exon 14 skipping mutations in NSCLC but do not cover EGFR. HLX48's dual-targeting design positions it as a potential option in the resistance setting.

The most structurally relevant ADC precedent is Daiichi Sankyo and AstraZeneca's fam-trastuzumab deruxtecan (Enhertu), a HER2-targeting ADC that received US FDA tumor-agnostic approval in 2024 for HER2-positive solid tumors with IHC3+ expression. That approval established a regulatory pathway for a single ADC to be approved across multiple histologies based on a shared biomarker. If HLX48 generates efficacy signals across EGFR- and c-MET-expressing tumor types in early clinical testing, a similar tumor-agnostic development strategy would be a plausible path forward.

This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/

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