Phase 3 Trial Launches for Ifinatamab Deruxtecan in Advanced Prostate Cancer Patients
Daiichi Sankyo and Merck have announced the initiation of IDeate-Prostate01, a global Phase 3 clinical trial evaluating the investigational drug ifinatamab deruxtecan (I-DXd) in patients with metastatic castration-resistant prostate cancer (mCRPC) who have experienced disease progression during or following treatment with androgen receptor pathway inhibitors (ARPIs). The study will assess the safety and efficacy of I-DXd compared to the current standard-of-care chemotherapy, docetaxel, in this heavily pretreated patient population.
A Next-Generation Antibody-Drug Conjugate Targeting B7-H3
Ifinatamab deruxtecan is a potential first-in-class antibody-drug conjugate (ADC) specifically engineered to target B7-H3, a surface protein overexpressed in many solid tumors, including prostate cancer. The investigational ADC is built using Daiichi Sankyo’s proprietary DXd technology and represents one of the newest generation of targeted cancer therapies. It combines a monoclonal antibody directed against B7-H3 with a potent topoisomerase I inhibitor payload, designed to deliver chemotherapy directly to cancer cells while minimizing off-target toxicity.
Discovered by Daiichi Sankyo, I-DXd is being co-developed with Merck (known as MSD outside of North America) as part of a broader strategic collaboration between the two companies. The IDeate-Prostate01 trial marks a significant advancement in the B7-H3 ADC development program and underscores the shared commitment of both companies to addressing difficult-to-treat cancers.
Addressing a Pressing Clinical Need in Prostate Cancer
Prostate cancer remains one of the most prevalent malignancies among men worldwide. While localized prostate cancer boasts a five-year survival rate above 90%, that figure drops precipitously to approximately 31% for metastatic disease. Metastatic castration-resistant prostate cancer represents the most advanced and lethal form of the disease, defined by progression despite androgen deprivation therapy and subsequent ARPI treatment.
Current treatment strategies for mCRPC typically begin with ARPIs such as enzalutamide or abiraterone, followed by taxane-based chemotherapy, most commonly docetaxel. However, the therapeutic benefit of docetaxel in this setting is limited by poor tolerability and modest efficacy. Many patients, particularly those who have received multiple prior treatments, fail to receive additional lines of therapy, often due to declining performance status or cumulative toxicity. This has created an urgent need for more effective and tolerable treatments for this population.
“Despite the emergence of new therapies, the current treatment landscape for patients with metastatic castration-resistant prostate cancer is challenging,” said Dr. Mark Rutstein, Head of Therapeutic Area Oncology Development at Daiichi Sankyo. “There is a critical need for new treatments. 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 disease progression during or after ARPI therapy.”
Building on Early Clinical Success
The Phase 3 IDeate-Prostate01 trial is based on encouraging results from the earlier IDeate-PanTumor01 Phase 1/2 study. Data from that trial, presented at both the 2022 and 2023 European Society for Medical Oncology (ESMO) Congresses, demonstrated promising anti-tumor activity and a manageable safety profile in heavily pretreated patients with mCRPC. These patients had exhausted standard treatment options, making them a highly refractory population.
In the IDeate-PanTumor01 study, ifinatamab deruxtecan showed objective responses in mCRPC patients whose disease had progressed after ARPIs and chemotherapy, suggesting the potential of the agent to offer meaningful clinical benefit. The drug’s design, targeting the immune checkpoint protein B7-H3, is particularly compelling given B7-H3’s association with poor prognosis, immune evasion, and therapeutic resistance in prostate cancer.
Dr. Marjorie Green, Senior Vice President and Head of Oncology Global Clinical Development at Merck Research Laboratories, emphasized the significance of this new trial within the broader scope of the ADC’s development. “IDeate-Prostate01 marks the initiation of the third pivotal trial in the ifinatamab deruxtecan program and reinforces our commitment to addressing critical unmet needs for patients,” she said. “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.”
Study Design and Objectives
The Phase 3 IDeate-Prostate01 study is a randomized, multicenter, open-label clinical trial. It will enroll patients with mCRPC who have experienced disease progression during or after ARPI therapy. Participants will be randomly assigned to receive either ifinatamab deruxtecan or docetaxel, with the primary endpoint being radiographic progression-free survival (rPFS). Key secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DoR), safety, and patient-reported outcomes related to quality of life and treatment tolerability.
By directly comparing I-DXd to docetaxel—the current standard chemotherapy—this trial seeks to determine whether the novel ADC can deliver superior outcomes with fewer side effects, potentially shifting the treatment paradigm in advanced prostate cancer.
A Broader B7-H3 Strategy
The IDeate-Prostate01 study is part of Daiichi Sankyo and Merck’s broader strategy to develop ifinatamab deruxtecan across multiple tumor types. The drug is currently being evaluated in additional pivotal studies, including those targeting non-small cell lung cancer (NSCLC) and other B7-H3-expressing solid tumors. As the third pivotal trial in the global I-DXd program, this prostate cancer study builds on the growing body of evidence supporting the role of B7-H3 as a viable therapeutic target.
As more patients are enrolled in the IDeate-Prostate01 trial, the oncology community will be closely monitoring the results for indications that ifinatamab deruxtecan can provide a meaningful survival benefit with a manageable safety profile. The need for alternatives to taxane chemotherapy in mCRPC is substantial, particularly for patients who have limited options following ARPI therapy.
If successful, this trial could position I-DXd as a new standard of care for a difficult-to-treat segment of the prostate cancer population. Furthermore, the development of a B7-H3-targeting ADC may pave the way for similar agents in other cancer types with high unmet need.
The launch of the IDeate-Prostate01 Phase 3 trial represents a significant milestone in the evolution of prostate cancer therapeutics. Backed by two leading pharmaceutical companies, Daiichi Sankyo and Merck, the study aims to validate ifinatamab deruxtecan as a new treatment option for patients with advanced prostate cancer who have progressed beyond hormone therapy. Should the trial’s results replicate the promising findings from earlier studies, it could signal a major step forward in the development of targeted antibody-drug conjugates for solid tumors.
