Shanghai Henlius Biotech, the HKEX-listed Chinese biopharmaceutical company, has registered a first-in-human Phase I clinical trial for HLX3902, a trispecific antibody designed to redirect T cells against STEAP1-expressing tumours by simultaneously delivering both primary and co-stimulatory activation signals. The trial, registered on ClinicalTrials.gov as NCT07533708, marks Henlius's entry into the co-stimulatory T-cell engager space and positions the company alongside a small but growing cohort of developers attempting to improve on the bispecific TCE format that has dominated immuno-oncology investment for the past decade.
The Phase Ia study is an open-label, sequential dose-escalation trial enrolling approximately 48 adults with metastatic castration-resistant prostate cancer (mCRPC) or other advanced solid tumours, including non-small cell lung cancer and gastric cancer, who have progressed after standard therapy. mCRPC-specific eligibility requires prior treatment with at least one novel androgen receptor pathway inhibitor and one or two taxane-based regimens, along with ongoing surgical or medical castration. Primary endpoints are dose-limiting toxicities within the first treatment cycle and the maximum tolerated dose. Secondary measures include objective response rate, PSA response, progression-free survival, pharmacokinetics, immunogenicity, and pharmacodynamic biomarkers — specifically peripheral cytokine levels and T-cell activation and proliferation markers consistent with the molecule's proposed mechanism. Primary completion is listed for Q2 2027, with overall study completion expected in Q2 2028. Primary completion data from NCT07533708 are expected in Q2 2027, with full study completion in Q2 2028.
The scientific rationale for HLX3902 rests on a recognised limitation of conventional bispecific TCEs. Standard CD3-engaging bispecifics deliver only Signal 1 — TCR/CD3 complex engagement — which, in the absence of co-stimulation, can drive T-cell anergy or exhaustion rather than sustained cytotoxic activity. This is particularly relevant in mCRPC, an immunologically cold tumour with a suppressive microenvironment that has proven resistant to checkpoint blockade. By incorporating a CD28-binding arm alongside anti-STEAP1 and anti-CD3 arms, HLX3902 aims to deliver Signal 2 simultaneously, promoting T-cell proliferation, upregulating survival factors, and sustaining effector function. The trial's pharmacodynamic endpoints — monitoring IL-2, IL-6, TNF-α, IFN-γ, and T-cell activation markers — are designed to test whether this co-stimulatory mechanism operates as intended in humans. HLX3902 appears to have been developed internally on what Henlius describes as a proprietary trispecific TCE platform, the same architecture used for HLX3901, a DLL3-targeting tetraspecific engager in development for small cell lung cancer. No licensing agreements or academic origin have been publicly disclosed for the molecule.