Soon to be Phase 1 for ICP-B381, a New Bispecific Antibody-Drug Conjugate for mCPRC

A new antibody-drug conjugate has received clearance to enter clinical trials in China with a double strategy for prostate cancer: instead of targeting PSMA or STEAP1, ICP-B381 targets both.

The experimental bispecific ADC combines a humanised antibody recognising PSMA and STEAP1 with a proprietary cytotoxic payload connected through an irreversible linker. Both proteins are strongly associated with prostate cancer and have relatively limited expression in normal tissues, but their expression can vary considerably between cancer cells.

That heterogeneity is precisely the problem ICP-B381 is designed to address. A conventional PSMA-targeted treatment depends on sufficient PSMA being present, while a STEAP1-targeted treatment has the equivalent vulnerability to loss or low expression of STEAP1. ICP-B381 can bind cells expressing either target. In principle, this could broaden the population of tumour cells exposed to the ADC and make escape through loss of a single antigen more difficult.

The preclinical results from animal models are striking. In a 22Rv1 prostate cancer xenograft characterised by low PSMA and very low STEAP1 expression, ICP-B381 produced dose-dependent tumour inhibition. At 1 mg/kg, tumour-growth inhibition was reported at approximately 94%, compared with about 81% for the corresponding STEAP1 ADC and 73% for the PSMA ADC at the same dose. No obvious treatment-related loss of body weight was observed.

The dose-response experiment provides another useful piece of information. ICP-B381 produced approximately 20% tumour-growth inhibition at 0.1 mg/kg, 31% at 0.3 mg/kg and about 90% at 1 mg/kg in the reported model, demonstrating a strong dose-dependent effect despite low expression of its targets.

The company has also reported activity in tumour models with low expression of both antigens and says the bispecific ADC performed better than a clinical-stage comparator in those experiments.

The Chinese regulatory authority has now cleared the Investigational New Drug application, allowing ICP-B381 to enter human testing in solid tumours including prostate cancer. A US IND filing has also been planned for September 2026.

Source.