Study of Ifinatamab Deruxtecan in De Novo or Treatment-Emergent Neuroendocrine Prostate Cancer

PRIMARY OBJECTIVE: I. To determine the objective response rate of I-DXd in de novo or treatment-emergent metastatic neuroendocrine prostate cancer. SECONDARY OBJECTIVES: I. To determine the median duration of response. II. To estimate the median radiographic progression-free survival and 6- and 12- month radiographic progression-free survival rates by investigator assessment. III. To evaluate the safety of I-DXd in patients with neuroendocrine prostate cancer. IV. To evaluate the PSA50 and PSA90 response rate in the subset of patients with baseline serum PSA greater than 5 ng/mL. V. To estimate the median overall survival (OS) of patients with de novo and t-NEPC treated with I-DXd. VI. To evaluate the molecular response as defined by a greater than 50% reduction from baseline in circulating tumor DNA (ctDNA) fraction. VII. To determine the molecular complete response rate as conversion from detectable ctDNA at baseline to undetectable while on study. EXPLORATORY OBJECTIVES: I. To evaluate the change in expression of B7-H3 and other cell surface antigens during the course of treatment by circulating biomarker assessment. II. To evaluate the association between efficacy outcomes (at the per-participant and per-lesion level) and baseline tumor tissue markers including histopathologic classification and tissue expression of B7-H3 as measured by Immunohistochemistry (IHC). using a central laboratory. III. To measure circulating immune cell subsets during the course of treatment and correlate with clinical outcomes. IV. To evaluate for intra-tumoral heterogeneity and co-expression of B7-H3 and other surface antigens using multiplex proteomic profiling with imaging mass cytometry and association with clinical outcomes. V. To evaluate patterns of response and progression by baseline and on-treatment molecular imaging.