Exploration of Drug Science

Table 5. Analysis of next-generation BiTEs in metastatic prostate cancer: engineering innovations and target profiles.

NCT number		Phase	Sponsor	Recruitment status	Description	Unique feature/Strategic advantage
1	NCT04104607	I	University Hospital Tuebingen	Recruiting	Anti-PSMA × CD3 CC-1	A foundational PSMA × CD3 construct used to establish safety profiles and manage CRS with IL-6 blockade prophylaxis, providing a benchmark for next-generation molecules.
2	NCT04221542	I	Amgen	Recruiting	AMG 509/anti-STEAP1 × CD3	Pivots to STEAP1, an antigen highly expressed in mCRPC, to overcome tumor heterogeneity and potential resistance to PSMA-targeted therapies. A leading candidate with a dedicated Phase III program.
3	NCT04702737	I	Amgen	Completed	AMG 757/anti-DLL3 × CD3	Targets DLL3, a key marker for NEPC, addressing a highly aggressive, treatment-resistant subtype with limited options.
4	NCT05125016	I/II	Regeneron Pharmaceuticals	Recruiting	REGN4336/anti-PSMA × CD28 + cemiplimab	Dual-costimulatory strategy: Engages CD28 for potent “Signal 2” T-cell activation alongside CD3 (“Signal 1”), and is rationally combined with a PD-1 inhibitor to prevent subsequent exhaustion.
5	NCT04740034	I	Amgen	Terminated	AMG 340 anti-PSMA × CD3	Developed as a next-generation anti-PSMA BiTE, likely incorporating optimizations in affinity, stability, or manufacturing over earlier constructs like AMG 160.
6	NCT04898634	I	Janssen Research & Development	Recruiting	JNJ-78278343 anti KLK2	Explores KLK2 as a novel target, diversifying the antigen landscape beyond PSMA and STEAP1. Features subcutaneous administration, a significant improvement in patient convenience over IV infusion.
7	NCT05369000	I	Lava Therapeutics	Terminated	LAVA-1207 anti-PSMA × γδ	Innovative mechanism: Engages Vγ9Vδ2 T cells, which have inherent tumor-homing and MHC-independent cytotoxicity, potentially offering a safer and more effective alternative to αβ T-cell redirection.
8	NCT06691984	III	Amgen	Recruiting	Bispecific STEAP1 × CD3 TCE	This pivotal Phase III trial positions STEAP1-targeting BiTEs as a potential new standard of care in mCRPC, directly testing their efficacy against established therapies like cabazitaxel.

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NCT: National Clinical Trial; BiTEs: bispecific T-cell engagers; CRS: cytokine release syndrome; DLL3: delta-like ligand 3; KLK2: kallikrein 2; mCRPC: metastatic castration-resistant prostate cancer; NEPC: neuroendocrine prostate cancer; SMA: prostate-specific membrane antigen; STEAP1: six-transmembrane epithelial antigen of the prostate 1; TCE: T-cell engager. Adapted from Meng et al. [6] with added technical and strategic analysis (CC-BY).

Declarations

Author contributions

DKN: Conceptualization, Writing—original draft, Writing—review & editing, Software, Methodology. VB: Investigation, Software. IJK: Visualization, Investigation. XZ: Supervision, Validation, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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