Zanzalintinib in Men With Aggressive Variant Prostate Cancer

This is a multi-center single arm phase II study to evaluate the antitumor activity of zanzalintinib 60mg orally (PO) once daily in subjects with AVPC. Zanzalintinib may continue until radiographic progression (or beyond), intolerable adverse events, or withdrawal of consent. As long as the subject is clinically stable, subjects may receive study treatment even after radiographic progression, until they are no longer clinically benefiting from the study treatment in the opinion of the treating Investigator, or they need subsequent systemic anticancer treatment or other urgent tumor directed medical intervention to prevent life-threatening complications. This study will use a 2-stage group-sequential design for enrollment. The first stage will consist of enrolling 15 subjects. No more than 5 of the first 15 subjects can have received chemotherapy in the castrate- resistant setting.