A Study of Risvutatug Rezetecan in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)

A Phase 3 Randomized Study to Evaluate the Safety and Efficacy of Risvutatug Rezetecan, a B7-H3 Antibody Drug Conjugate (ADC) in Participants With Metastatic Castration-resistant Prostate Cancer (EMBOLD Prostate-302)

This study aims to evaluate how well risvutatug rezetecan (Ris-Rez) works in treating prostate cancer compared to best supportive/standard of care (BSC) which may include a hormone therapy with an androgen receptor pathway inhibitors (ARPI), by checking whether it makes cancers smaller or disappear completely, if it helps participants live longer, and/or feel better. The study is also assessing whether Ris-Rez is safe and tolerated well by participants and aims to provide a better understanding of the side effects of the drug.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoplasms, Prostate
• Intervention / Treatment: Drug: Abiraterone; Drug: Enzalutamide; Biological: Risvutatug rezetecan (Ris-Rez); Drug: Prednisone; Drug: Prednisolone

• Study Type: Interventional
• Enrollment (Estimated): 684
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants ≥18 years of age
• Has histologically or cytologically confirmed adenocarcinoma of the prostate.
• Has an Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1, with no deterioration in the 2 weeks before randomization.
• Has a life expectancy of at least 4 months.
• Has adequate organ function

Exclusion Criteria:

• Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate, mixed histologies or any histology different from adenocarcinoma.
• Participants with known mismatch repair deficient (dMMR)/MSI-H/TMB-H status and eligible for immune checkpoint inhibitor therapy,
• Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix] with no evidence of metastatic disease.
• Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 28 days before the date of randomization,
• Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
• Known active infectious diseases requiring systemic treatment or known human immunodeficiency virus (HIV)
• Has untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
• Has received systemic immunosuppressive agents within 30 days prior to first dose of study intervention (or requires long-term administration [30 days or longer]).
• Has received any prior therapy with an ADC with a topoisomerase 1 inhibitor (TOPO1-inhibitor) payload

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risvutatug rezetecan (Ris-Rez); Participants will receive Risvutatug rezetecan (Ris-Rez).	Biological: Risvutatug rezetecan (Ris-Rez); Risvutatug rezetecan (Ris-Rez) will be administered.
Active Comparator: Standard of Care; Participants will receive physician's choice of best supportive/standard of care (BSC), with or without androgen receptor pathway inhibitors (ARPI) Enzalutamide, Abiraterone (with Prednisone or Prednisolone).	Drug: Abiraterone; Abiraterone will be administered.; Drug: Enzalutamide; Enzalutamide will be administered.; Drug: Prednisone; Prednisone will be administered along with Abiraterone.; Drug: Prednisolone; Prednisolone will be administered along with Abiraterone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression-Free Survival (rPFS) per PCWG3 by BICR	rPFS is defined as time from randomization to the first documented radiographic disease progression, per Prostate cancer clinical trials working group 3 (PCWG3) as assessed by Blinded Independent Central Review (BICR) or death due to any cause, whichever occurs first.	Up to approximately 169 weeks
Overall Survival (OS)	OS is defined as the time from randomization to date of death by any cause.	Up to approximately 169 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Pain Progression (TTPP)		Up to approximately 169 weeks
rPFS by Investigator assessment	rPFS is defined as time from randomization to the first documented radiographic disease progression per PCWG3 as assessed by Investigator or death due to any cause, whichever occurs first.	Up to approximately 169 weeks
Confirmed Objective Response Rate (cORR)	cORR is defined as the percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) per PCWG3 by BICR.	Up to approximately 169 weeks
Duration of Response (DoR)	DoR defined as the time from the date of first confirmed response (CR or PR) to the date of first documented PD per PCWG3 as assessed by BICR or death due to any cause, whichever comes first.	Up to approximately 169 weeks
Time to Prostate-specific antigen (PSA) progression	Time to PSA progression is defined as the time from randomization to PSA progression according to PCWG3 criteria.	Up to approximately 169 weeks
Prostate-specific antigen 50 (PSA50) response	PSA50 is defined as the proportion of participants having a ≥50% post-baseline PSA reduction from baseline with a consecutive confirmation assessment at least 3 weeks later.	Up to approximately 169 weeks
Time to first Symptomatic Skeletal-Related Event (SSRE)	Time to first SSRE is defined as the time from randomization to first occurrence of any of the following symptomatic skeletal-related events: Use of EBRT to prevent or relieve skeletal symptoms .; New symptomatic pathological bone fracture (vertebral or non-vertebral).; New symptomatic spinal cord compression.; Tumor-related orthopedic surgical intervention	Up to approximately 169 weeks
Number of participants with adverse event (AEs), serious adverse event (SAEs), Adverse event of special interest (AESIs) by severity		Up to approximately 169 weeks
Number of participants with AEs leading to dose modifications or study intervention discontinuation		Up to approximately 169 weeks
Serum concentration of Ris-Rez (conjugated antibody and payload)		Up to approximately 84 days
Number of participants with Antidrug antibody (ADA) and Neutralizing Antibody (NAb) against Ris-Rez		Up to approximately 169 weeks
Titers of ADA against Ris-Rez		Up to approximately 169 weeks
Participant-reported experience on study treatment	Number of participants who reported their experience with study treatment using validated questionnaires will be measured	Up to approximately 169 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): September 22, 2026
• Primary Completion (Estimated): December 19, 2029
• Study Completion (Estimated): December 19, 2029

Study Registration Dates

• First Submitted: August 28, 2026
• First Submitted That Met QC Criteria: August 28, 2026
• First Posted (Actual): September 3, 2026

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Antibody-Drug Conjugate; Enzalutamide; Abiraterone; Metastatic Castration-resistant Prostate Cancer; GSK5764227; Ris-Rez; Risvutatug rezetecan; EMBOLD Prostate-302
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Pregnadienediols; Prednisone; Prednisolone; abiraterone; enzalutamide
• Other Study ID Numbers: 300145; 2026-525558-13-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No