IDeate-Prostate01: A phase 3, randomized, open-label study of ifinatamab deruxtecan versus docetaxel in participants with previously treated metastatic castration-resistant prostate cancer.

Abstract

TPS294 Background: Standard treatments for metastatic castration-resistant prostate cancer (mCRPC) include androgen deprivation therapy (ADT) plus systemic androgen receptor pathway inhibitors (ARPIs), taxanes, radiopharmaceuticals, or targeted therapies. Despite these treatment options, disease progression is inevitable. Treatments that improve upon the outcomes shown with currently available options are urgently needed. B7-H3, a type I transmembrane protein, is overexpressed in prostate cancer and associated with poor prognosis and unresponsiveness to certain treatments. Ifinatamab deruxtecan (I-DXd; MK-2400/DS-7300a) is a B7-H3-directed antibody-drug-conjugate, with a plasma-stable tetrapeptide-based cleavable linker and the potent topoisomerase I inhibitor payload DXd. In preclinical models, I-DXd exerted potent antitumor activity in B7-H3-expressing tumors and acceptable pharmacokinetics and safety. Preliminary results from the first-in-human phase 1/2 IDeate-PanTumor01 study of I-DXd demonstrated antitumor activity and manageable safety in multiple solid tumors, including heavily pretreated mCRPC. Methods: IDeate-Prostate01 is a phase 3, randomized, open-label study. Eligible participants must have: histologically or cytologically confirmed mCRPC; documented prostate-specific antigen (PSA) or radiologic disease progression; and have received 1 or 2 previous ARPIs for metastatic or nonmetastatic hormone-sensitive prostate cancer or CRPC. Prior taxane chemotherapy for mCRPC is not allowed. Approximately 1,440 participants will be randomized 1:1 (~720 participants per treatment arm) to I-DXd at 12 mg/kg intravenously (IV), once every 3 weeks (q3w), or docetaxel at 75 mg/m 2 IV, q3w (with prednisone/prednisolone at 10 mg/day orally, or per label). Randomization will be stratified by metastatic site (liver vs. bone only vs. other), geographic region (Region 1 [Australia, European Union, Israel, Japan, South Korea, Switzerland, United Kingdom, and United States of America] vs. rest of the world), B7-H3 expression (high vs. low vs. unevaluable), and prior prostate-specific membrane antigen-targeted radionuclide therapy (yes vs. no). Dual primary end points are overall survival and radiographic progression-free survival. Secondary end points include time to first subsequent therapy, objective response, duration of response, time to pain progression, time to PSA progression, PSA response, time to first symptomatic skeletal-related event, and safety and tolerability. Recruitment is ongoing. Previously presented at 26th Annual Meeting of the Society of Urologic Oncology; December 2–5, 2025; Phoenix, AZ. Clinical trial information: NCT06925737 .