Phase 3 trial launches of ifinatamab deruxtecan vs chemotherapy in mCRPC

The first patient has been dosed in the phase 3 IDeate-Prostate01 trial (NCT06925737), evaluating the safety and efficacy of ifinatamab deruxtecan vs docetaxel for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), Daiichi Sankyo announced in a news release.¹

Primary completion of the study is anticipated for June 2028.

Ifinatamab deruxtecan is an investigational B7-H3 directed DXd antibody drug conjugate.

“Despite the emergence of new therapies, the current treatment landscape for patients with metastatic castration-resistant prostate cancer is challenging, and there is a need for new treatments,” said Mark Rutstein, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo, in the news release.¹ “Following the promising results seen in our earlier phase trial, IDeate-Prostate01 has been initiated to evaluate whether ifinatamab deruxtecan may replace standard taxane-based chemotherapy as a potential treatment strategy in patients with metastatic castration-resistant prostate cancer with disease progression during or after treatment with androgen receptor pathway inhibitors [ARPIs].”

In total, the multicenter, open-label IDeate-Prostate01 trial plans to enroll approximately 1440 adult patients across clinical trial sites in North America, Europe, Asia, and Oceania. To be eligible for enrollment, patients need to have received prior treatment with 1 or 2 ARPIs and had their tumors progress during or after at least 8 weeks of treatment.

For the study, participants will be randomly assigned to receive 12 mg/kg of ifinatamab deruxtecan every 3 weeks or to 75 mg/m² of docetaxel every 3 weeks plus 10 mg prednisone per day.

The dual primary end points for the trial are overall survival (OS) and radiographic progression-free survival (rPFS). The trial’s secondary end points include objective response rate (ORR), time to first subsequent therapy, duration of response, time to pain progression, time to prostate-specific antigen (PSA) progression, PSA response, time to first symptomatic skeletal-related event, and safety. All end points will be assessed for up to 36 months.

Primary completion of the study is anticipated for June 2028.²

“IDeate-Prostate01 marks the initiation of the third pivotal trial in the ifinatamab deruxtecan development program and reinforces our commitment to addressing critical unmet needs for patients,” said Marjorie Green, MD, Senior Vice President and Head of Oncology, Global Clinical Development, Merck Research Laboratories.¹ “Our continued progress in the exploration of this potential first-in-class B7-H3 antibody drug conjugate in collaboration with Daiichi Sankyo speaks to our pursuit of novel science in the hopes of making a difference for patients in need of new options.”

Previous data on ifinatamab deruxtecan

The IDeate-Prostate01 trial is based on results from the phase 1/2 Ideate-PanTumor01 trial (NCT04145622), where ifinatamab deruxtecan demonstrated encouraging clinical activity in the subset of patients with pretreated mCRPC.

Data presented at the 2022 European Society of Medical Oncology (ESMO) Congress³ showed a response rate of 33% (95% CI, 21 to 47) in this subgroup (n = 54). Baseline live metastases were present in 46% of patients at baseline, and among these patients, 40% achieved a response to treatment.

Updated data were presented at the 2023 ESMO Congress,⁴ showing a confirmed ORR of 25% in this cohort. The median duration of response was 6.4 months (95% CI, 2.8 to 10.6). Additionally, the median PFS and OS were 4.8 months (95% CI, 3.9 to 5.9) and 13.5 months (95% CI, 10.3 to 16.6), respectively.

REFERENCES

1. IDeate-Prostate01 phase 3 trial of ifinatamab deruxtecan initiated in patients with pretreated metastatic castration-resistant prostate cancer. News release. Daiichi Sankyo. Published online and accessed June 18, 2025. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202506/20250618_E.pdf

2. A clinical study of ifinatamab deruxtecan (I-DXd) in people with metastatic prostate cancer (MK-2400-001). ClinicalTrials.gov. Last updated May 29, 2025. Accessed June 18, 2025. https://clinicaltrials.gov/study/NCT06925737

3. DS-7300 continues to show promising durable response in patients with several types of advanced cancer. News release. Daiichi Sankyo. September 10, 2022. Accessed June 18, 2025. https://daiichisankyo.us/press-releases/-/article/ds-7300-continues-to-show-promising-durable-response-in-patients-with-several-types-of-advanced-cancer

4. Patel MR. Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study. Presented at: 2023 European Society of Medical Oncology Congress. Madrid, Spain. October 20-24, 2023. https://cslide.ctimeetingtech.com/esmo2023/attendee/confcal_2/presentation/list?q=690P