IDeate-Prostate02: A phase 1/2, open-label umbrella substudy of ifinatamab deruxtecan-based treatment combinations or as monotherapy in participants with previously treated metastatic castration-resistant prostate cancer.

Abstract

TPS297 Background: There is a high unmet need for effective therapies to improve outcomes from metastatic castration-resistant prostate cancer (mCRPC). Ifinatamab deruxtecan (I-DXd; MK-2400/DS-7300a), a B7-H3-directed antibody-drug-conjugate with a plasma-stable tetrapeptide-based cleavable linker and the potent topoisomerase I inhibitor payload DXd, has antitumor activity in in-vitro and in-vivo models. A first-in-human phase 1/2 study of I-DXd demonstrated promising antitumor activity and encouraging duration of response in heavily pretreated participants with mCRPC, with a manageable safety profile. These results merit further clinical investigation of I-DXd-based investigational treatment combinations to identify benefit in patients with mCRPC. Methods: IDeate-Prostate02 is a phase 1/2, multicenter, open-label, umbrella substudy of I-DXd-based treatments. Participants with mCRPC, evaluable B7-H3, and previously treated with 1 or 2 androgen receptor pathway inhibitors (ARPIs) but no prior docetaxel for mCRPC, will be included. Two monotherapy arms, each with ~80 to ~120 participants, will enroll participants into the Efficacy Phase; Arm 1: docetaxel and Arm 2: I-DXd. Two I-DXd combination arms will enroll participants into the Safety Lead-in (n~10), followed by Efficacy (n~50) phases: Arm 3: I-DXd+MK-5684, and Arm 4: I-DXd+ARPI. Administered treatments and stratification factors are in the Table. Primary end points are safety, tolerability, and prostate-specific antigen response rate (≥50% reduction) for the Efficacy Phase, and safety and phase 2 dose recommendations for the Safety Lead-in. Key secondary end points include objective response and survival evaluations. Recruitment is ongoing. Previously presented at 26th Annual Meeting of the Society of Urologic Oncology; December 2–5, 2025; Phoenix, AZ. Clinical trial information: NCT06863272 . Arm Administered Treatments Arm 1 Docetaxel at 75 mg/m 2 IV q3w with prednisone/prednisolone at 10 mg/day po or per label Arm 2 I-DXd at 12 mg/kg IV q3w Arm 3 I-DXd at 8, 10, or 12 mg/kg IV q3w + opevesostat at 5 mg po bid with fludrocortisone at 0.1 mg po qd, dexamethasone (adjusted as required) at 1.5 mg po qd, and hydrocortisone at 100 mg intramuscularly or po Arm 4 I-DXd at 8, 10, or 12 mg/kg IV q3w + ARPI as either abiraterone acetate at 1000 mg po qd with prednisone/prednisolone at 10 mg/day po or per label, or enzalutamide at 160 mg po qd (prior treatment dependent) Stratification for randomization Subgroups  B7-H3 expression High vs. low  Metastasis location Liver vs. bone only vs. other bid, twice daily; IV, intravenously; po, orally; q3w, every 3 weeks; qd, once daily.