Zanzalintinib for Metastatic Castration-Resistant Prostate Cancer

Zanzalintinib is a new investigational drug showing activity in metastatic castrate-resistant prostate cancer (mCRPC), particularly in patients with soft tissue or visceral metastases who have progressed on prior treatment. A single-arm Phase II trial is evaluating whether zanzalintinib is effective for this difficult-to-treat population. Participants can stay in the study for up to 24 months if they experience clinical benefit.

Prostate cancer initially responds to androgen deprivation therapy and androgen receptor pathway inhibitors (ARPI), but eventually becomes castrate-resistant with poorer outcomes. The drug works by starving tumors of blood supply through VEGFR2 inhibition while blocking MET-driven metastasis and AXL/MERTK-mediated immune suppression. This multi-targeted approach prevents cancers from developing resistance through bypass pathways. Preclinical data also suggests zanzalintinib can convert immunologically “cold” tumors into “hot” ones, which explains why most trials combine it with PD-1/PD-L1 checkpoint inhibitors for enhanced effect.

This Phase 2 interventional study plans to enroll 19 participants, starting September 2026. The drug being tested is zanzalintinib for metastatic castration-resistant prostate cancer with soft tissue or visceral metastases.

Participants must have confirmed mCRPC with soft tissue or visceral metastases on CT or bone scans, prior treatment with an ARPI (abiraterone, enzalutamide, apalutamide, or darolutamide).

Clinical trial.