HLX43 Nets FDA Orphan Drug Designation in Thymic Epithelial Tumors

The PD-L1–directed antibody-drug conjugate (ADC) HLX43 has received orphan drug designation from the FDA for the treatment of patients with thymic epithelial tumors.1

At a data cutoff of June 28, 2025, findings from a phase 1 study (NCT06115642) presented during the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer demonstrated that patients with non–small cell lung cancer (NSCLC) who received HLX43 (n = 54) achieved an overall response rate (ORR) of 37.0% (95% CI, 24.3%-51.3%); all responses were partial.2 The disease control rate was 87.0% (95% CI, 75.1%-94.6%). The median progression-free survival (PFS) was 5.4 months (95% CI, 4.0-5.8).

Notably, patients with EGFR wild-type NSCLC (n = 15) experienced an ORR of 46.7% (95% CI, 21.3%-73.4%). The ORR among these patients who received HLX43 at 2.5 mg/kg (n = 5) was 60.0% (95% CI, 14.7%-94.7%). Patients with a PD-L1 combined positive score of less than 1% (n = 21) experienced an ORR of 38.1% (95% CI, 18.1%-61.6%).

“Thymic epithelial tumors remain a challenging and understudied disease area, especially for patients with advanced thymic carcinoma who currently have very limited treatment options,”Marina Garassino, MD, the leading principal investigator of the HLX43 Thymic Study in the US and a professor of medicine at the University of Chicago Medicine in Illinois, stated in a news release.1 “The encouraging preliminary efficacy observed with HLX43 brings new hope to patients with advanced thymic epithelial tumors. I’m pleased to see this innovative PD-L1 ADC receiving Orphan Drug Designation from the U.S. FDA, a milestone that further validates its potential to address a significant unmet medical need.”

What was the design of the phase 1 study?

The first-in-human study enrolled adult patients with histologically or cytologically confirmed advanced solid tumors in phase 1a and those with NSCLC that was refractory or not amendable to standard therapy in phase 1b. All patients were required to have measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

During phase 1a, patients received HLX43 at 0.5 mg (n = 3 to 6), 1.0 mg.kg (n = 3 to 6), 2.0 mg/kg (n = 3 to 6), 2.5 mg/kg (n = 3 to 6), 3.0 mg/kg (n = 3 to 6), or 4.0 mg/kg (n = 3 to 6) every 3 weeks. During phase 1b, patients with NSCLC were treated at 2.0 mg/kg (n = 20), 2.5 mg/kg (n = 20), or 3.0 mg/kg (n = 20) every 3 weeks.

The primary end points in phase 1a were the proportion of patients with dose-limiting toxicities and determining the maximum tolerated dose. In phase 1b, the primary end points were determining the recommended phase 2 dose and ORR.

What was the safety profile of HLX43?

In terms of safety, any-grade treatment-related adverse effects (TRAEs) were reported in all patients with NSCLC (n = 56). Grade 3 or higher TRAEs occurred at a rate of 46.4%; the most common grade 3 or higher TRAEs included anemia (19.6%), decreased white blood cell count (19.6%), decreased neutrophil count (16.1%), and decreased lymphocyte count (12.5%). TRAEs leading to treatment interruption (42.9%), discontinuation (8.9%), and reduction (17.9%) were reported. One patient died due to a TRAE.

More than 400 patients are enrolled globally in the phase 1 study, with enrollment progressing in countries including China, the US, Japan, and Australia.1 HLX43 is also being examined for the treatment of patients with multiple types of solid tumors, including cervical cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, nasopharyngeal cancer, colorectal cancer, and gastric or gastroesophageal junction adenocarcinoma. Currently, the agent is being evaluated both as monotherapy and as a combination component.

References

1. Henlius receives orphan drug designation for PD-L1 ADC HLX43 in the U.S. for thymic epithelial tumors. News release. Sanghai Henlius Biotech. October 20, 2025. Accessed October 21, 2025. https://www.henlius.com/en/NewsDetails-5517-26.html
2. Wang J. HLX43 first-in-human study data readout. Sanghai Henlius Biotech. September 6, 2025. Accessed October 21, 2025. https://www.henlius.com/upload/202509/10/HenliusWCLCHLX43HLX07HLX10Datareadout20250902.pdf