On June 17, the CDE official website announced that Henlius’ HLX3902 Injection has been approved for clinical trial in China, intended for the treatment of metastatic castration-resistant prostate cancer and other advanced solid tumors. According to the Insight database, HLX3902 is Henlius’ first trispecific antibody approved for clinical trial and the world’s first-in-class STEAP1×CD3×CD28 trispecific antibody to receive clinical trial clearance.
Prostate cancer typically presents as an “immune-cold” tumor—characterized by sparse T cell infiltration, low antigen presentation capacity, and an abundance of immunosuppressive factors—which limits the efficacy of immune checkpoint inhibitors such as PD-1 inhibitors. STEAP1 is highly expressed in over 85% of prostate tumors while being nearly absent in normal tissues, making it a highly specific therapeutic target. T cell engagers (TCEs) targeting STEAP1 can simultaneously bind CD3 on T cells and STEAP1 on tumors, redirecting T cells to kill tumor cells, and have demonstrated anti-tumor activity in various models. However, existing TCEs primarily rely on CD3-mediated primary activation signals, and T cells lacking co-stimulatory signals in the solid tumor microenvironment are prone to exhaustion, limiting sustained anti-tumor efficacy. The introduction of CD28 co-stimulatory signaling can enhance T cell persistence and functional maintenance through a “dual-signal” activation mechanism.
As a trispecific antibody, HLX3902 simultaneously activates CD3 and CD28 to enhance T cell killing of STEAP1-expressing tumor cells. By optimizing both the first (CD3) and second (CD28) T cell activation signals, it enhances T cell activation, proliferation, and survival, prolonging the duration of anti-tumor immune responses. This enables it to demonstrate excellent anti-tumor activity even in low T cell infiltration environments.
Preclinical studies have shown that HLX3902 induces target-dependent T cell activation and cytotoxicity, outperforming traditional CD3 bispecific TCEs at low effector-to-target cell ratios. Repeated antigen stimulation models indicate that its CD28 co-stimulatory signal enhances T cell activation, proliferation, and memory T cell expansion, thereby maintaining durable killing effects. In C4-2/hPBMC and abiraterone-resistant PDX/hPBMC in vivo models, HLX3902 demonstrated significantly enhanced anti-tumor activity, accompanied by increased T cell infiltration and functional improvement. Additionally, in cynomolgus monkey studies, HLX3902 exhibited good tolerability and a manageable safety profile.
Buy HLX3902 from China and save up to 80% on costs . no insurance needed . compare prices from a certified HongKong pharmacy .with fast shipping. Contact us now on WhatsApp to get the latest prices.
