Shanghai Henlius Biotech (HKEX: 2696) has received clearance to initiate a Phase I clinical trial of HLX3902, a trispecific T-cell engager antibody targeting STEAP1, CD3, and CD28, in patients with metastatic castration-resistant prostate cancer and other advanced solid tumors in Australia. The trial received approval from the relevant Human Research Ethics Committee and acknowledgement from the Therapeutic Goods Administration, clearing the path for first-in-human testing of a molecule the company said has demonstrated anti-tumor activity and an acceptable safety profile in preclinical studies.
HLX3902 is designed to bind simultaneously to three distinct proteins: STEAP1, expressed on the surface of prostate cancer cells, and the T-cell surface receptors CD3 and CD28. By engaging CD3, the antibody initiates cytotoxic T-cell activation against STEAP1-expressing tumor cells — a mechanism referred to as Signal 1. The simultaneous engagement of CD28 provides co-stimulatory signaling, or Signal 2, which the company said is intended to enhance T-cell proliferation, survival, and overall anti-tumor response.
This trispecific architecture distinguishes HLX3902 from conventional bispecific T-cell engagers, which typically engage only CD3 alongside a tumor-associated antigen. By incorporating CD28 co-stimulation into the same molecule, Henlius is attempting to address a recognized limitation of CD3-only engagers: insufficient T-cell persistence and activity in immunosuppressive solid tumor environments.
STEAP1 — Six-Transmembrane Epithelial Antigen of the Prostate 1 — is a cell-surface protein overexpressed in prostate cancer and, to varying degrees, in other solid tumors including colorectal, bladder, and lung cancers. Its restricted expression in normal tissues makes it an attractive target for tumor-directed immunotherapy. Henlius noted that as of the announcement date, no trispecific antibody targeting STEAP1, CD3, and CD28 has been approved globally, positioning HLX3902 as a novel entry into this mechanistic class.
Competitive context
Approved options for prostate cancer now include second-generation androgen receptor pathway inhibitors such as enzalutamide and abiraterone, PARP inhibitors including olaparib and niraparib in combination with abiraterone for patients with homologous recombination repair alterations, the PSMA-targeted radioligand therapy lutetium-177 vipivotide tetraxetan, and the alpha-emitting radium-223 dichloride for bone-predominant disease. Despite this range of agents, patients who progress through multiple lines of therapy have limited options, and resistance mechanisms remain incompletely understood.