Introduction:

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 I/II 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 (NCT06863272) 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 (Figure). Two monotherapy arms (Arm 1 [docetaxel] and Arm 2 [I-DXd]) will enroll participants into the Efficacy Phase, and 2 I-DXd combination arms (Arm 3: I-DXd+MK-5684; and Arm 4: I-DXd+ARPI [abiraterone acetate or enzalutamide; prior treatment dependent]) will enroll into the Safety Lead-in, followed by Efficacy Phase. Participants will be randomized (Efficacy Phase) or allocated (Safety Lead-in) to a treatment arm. 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.

Results:

Conclusion:

Funding: Funding for this study was provided by Daiichi Sankyo Company, Limited and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA