Phase 3 Open-Label Comparison of Ifinatamab Deruxtecan and Docetaxel in Metastatic Castration-Resistant Prostate Cancer

The primary objective of this Phase 3 study is to compare **Ifinatamab Deruxtecan** (I-DXd) to **docetaxel** in terms of overall survival (OS) in participants with **metastatic castration-resistant prostate cancer** (mCRPC). This is clinically relevant as OS is a critical endpoint in assessing the efficacy of cancer treatments, providing insights into the potential of I-DXd as a therapeutic option for mCRPC.

Secondary objectives include:

• Evaluating the time to first subsequent therapy or death (TFST) of participants treated with I-DXd compared to those treated with docetaxel.
• Assessing the objective response (OR) and duration of response (DOR) per Prostate Cancer Working Group (PCWG) Modified RECIST 1.1, as evaluated by blinded independent central review (BICR), in participants treated with I-DXd versus docetaxel.
• Evaluating the time to pain progression (TTPP) in participants treated with I-DXd compared to those treated with docetaxel.
• Assessing the time to prostate-specific antigen (PSA) progression in participants treated with I-DXd versus docetaxel.
• Evaluating the PSA response rate in participants treated with I-DXd compared to those treated with docetaxel.
• Assessing the time to first symptomatic skeletal-related event (SSRE) in participants treated with I-DXd versus docetaxel.
• Evaluating the safety and tolerability of I-DXd.

The clinical trial involves a total of **940 participants** diagnosed with **Metastatic Castration-Resistant Prostate Cancer**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including histologically- or cytologically-confirmed adenocarcinoma of the prostate, evidence of metastatic disease, and progression on androgen deprivation therapy. The trial does not include a vulnerable population. Participants have previously received treatment with androgen receptor pathway inhibitors and have recovered from adverse events related to prior anticancer therapies. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and safety of **Ifinatamab Deruxtecan** compared to **Docetaxel** in patients with **metastatic castration-resistant prostate cancer** (mCRPC). This is a Phase 3, open-label, randomized, controlled study. The primary objectives are to compare overall survival (OS) and radiographic progression-free survival (rPFS) between the two treatment groups. Secondary endpoints include time to first subsequent therapy (TFST), objective response rate (ORR), duration of response (DOR), time to pain progression (TTPP), time to prostate-specific antigen (PSA) progression, PSA response rate, time to first symptomatic skeletal-related events (SSRE), and the number of participants experiencing adverse events (AEs) or discontinuing treatment due to AEs.

The trial is expected to commence recruitment on June 30, 2025, and conclude by January 6, 2031. Participants will be involved in the study for a maximum treatment period of 33 days, with the possibility of early termination if they experience unacceptable toxicity, disease progression, or withdrawal of consent. The study will begin with a screening visit to confirm eligibility based on criteria such as histologically-confirmed adenocarcinoma of the prostate, evidence of metastatic disease, and prior treatment history. Following randomization, participants will receive either Ifinatamab Deruxtecan or Docetaxel, administered intravenously.

Study visits will be scheduled to monitor treatment response and safety, including regular assessments of tumor progression and adverse events. The end-of-study visit will occur after the final treatment cycle, where comprehensive evaluations will be conducted to assess the primary and secondary endpoints. Participants may be withdrawn from the study if they do not meet the inclusion criteria, experience severe adverse reactions, or choose to discontinue participation. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Ifinatamab Deruxtecan**, an experimental medication, which is a **solution for infusion**. This biological product is administered via **intravenous use**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 12 mg/kg. The treatment period for Ifinatamab Deruxtecan is limited to one day. The active substance, Ifinatamab Deruxtecan, is a protein-based compound, specifically categorized as "Protein - Other". The sponsor product code for this medication is MK-2400, and it is developed by Merck & Co. Inc.

**Docetaxel** serves as the comparator treatment in this study. It is a chemical compound administered as a **PHF00230MIG** form via **intravenous use**. The maximum daily dose is 75 mg/m², with a total maximum dose of 750 mg/m² over a treatment period of 30 days. Docetaxel is a well-established chemotherapeutic agent used in the treatment of various cancers, including metastatic castration-resistant prostate cancer (mCRPC).

In addition to the primary treatments, the study includes the use of **Betamethasone Sodium Phosphate** and **Prednisolone** as auxiliary medications. Betamethasone Sodium Phosphate is administered orally in a **PHF00059MIG** form, with a maximum daily dose of 10 mg and a total maximum dose of 2200 mg over a 33-day period. Prednisolone, also administered orally, is provided in a **PHF00245MIG** form, with the same dosing schedule as Betamethasone Sodium Phosphate. Both substances are chemical compounds used to manage inflammation and immune responses.

Additional auxiliary treatments include **Buclizine Hydrochloride, Paracetamol, and Codeine Phosphate**, which are administered in a **PHF00082MIG** form. These substances are used for symptomatic relief and are categorized as chemical compounds. The administration route is specified as "other use," indicating non-standard administration methods. The study also involves the use of **Glucocorticoids**, **Antihistamines for Systemic Use**, **Serotonin (5HT3) Antagonists**, and **Other Antiemetics** as auxiliary treatments, all administered in various pharmaceutical forms with unspecified routes, categorized under "other use". These auxiliary treatments are chemical compounds used to manage side effects and enhance participant comfort during the trial.

The efficacy of the clinical trial will be assessed using primary and secondary endpoints. The primary endpoints include **Overall Survival (OS)** and **Radiographic Progression-Free Survival (rPFS)**, which will be evaluated according to the Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). These assessments will be conducted by a blinded independent central review (BICR) to ensure objectivity and accuracy in participants with metastatic castration-resistant prostate cancer (mCRPC).

Secondary endpoints will provide additional insights into the efficacy of the treatment. These include Time to First Subsequent Therapy (TFST), Objective Response Rate (ORR), Duration of Response (DOR), Time to Pain Progression (TTPP), Time to Prostate-Specific Antigen (PSA) Progression, PSA Response Rate, Time to First Symptomatic Skeletal-Related Events (SSRE), and the number of participants experiencing one or more adverse events (AEs) or discontinuing study treatment due to an AE. These parameters will be measured at various time points throughout the trial to capture a comprehensive picture of the treatment's impact on the disease.