voxalatamab (JNJ-63898081)

JNJ-081 dosing led to transient declines in PSA in patients with mCRPC. CRS and IRR could be partially mitigated by SC dosing, step-up priming, and a combination of both strategies. T cell redirection for prostate cancer is feasible and PSMA is a potential therapeutic target for T cell redirection in prostate cancer.

On progression, he was reinitiated on pembrolizumab and experienced an exceptional second response, with his prostate-specific antigen falling from a high of 20.01 to undetectable after 6 weeks and remaining undetectable for >11 months. To our knowledge, this represents the first reported case of bispecific T-cell engager-mediated re-sensitization to checkpoint inhibitor therapy in any cancer.

P1 | " This Phase 1 Dose Escalation Study evaluated JNJ-081 in mCRPC participants (pts) who progressed after novel androgen targeting therapy (eg, abiraterone, enzalutamide or apalutamide). JNJ-081 demonstrated transient decreases in PSA in mCRPC patients. Grade 2 CRS was observed at higher doses and was partially mitigated by SC and step-up dosing. ADA resulting in decreased exposure occurred in the majority of pts treated SC."

In addition, JNJ-63898081 was able to effectively cause T cell dependent cytotoxicity of an enzalutamide-resistant LNCaP-AR cell line. Collectively, these data provided the impetus to initiate clinical testing of JNJ-63898081 for the treatment of prostate cancer. Funding Acknowledgments: Janssen R&D