Phase 3 Trial Tests a New B7-H3 Strategy in Advanced Prostate Cancer

A new phase 3 clinical trial is preparing to evaluate risvutatug rezetecan, or Ris-Rezor GSK5764227, in men with metastatic castration-resistant prostate cancer (mCRPC), an advanced form of prostate cancer that continues to progress despite androgen-deprivation treatment. The study, called EMBOLD Prostate-302, will compare this experimental therapy with best supportive or standard care, potentially including the androgen-receptor pathway inhibitors enzalutamide or abiraterone, used with prednisone or prednisolone. The trial is planned to enrol approximately 684 participants.

Ris-Rez is an antibody–drug conjugate (ADC) directed against B7-H3, also known as CD276. An ADC combines a targeted antibody with a cell-killing drug payload. The antibody is designed to bind B7-H3 on the surface of tumour cells, allowing the conjugate to be internalised and deliver its payload inside the cancer cell. Ris-Rez uses a topoisomerase-inhibitor payload, a type of cytotoxic mechanism that interferes with DNA processing and can lead to tumour-cell death. (We have talked about risvutatug rezetecan Phase 1/2 trial here)

The biological rationale for targeting B7-H3 in prostate cancer is substantial. B7-H3 is frequently expressed at higher levels in prostate tumours than in normal prostate tissue and has been associated in several studies with aggressive disease, tumour progression, and poorer outcomes. Unlike some tumour markers that are lost as prostate cancer evolves, B7-H3 appears to be broadly retained during progression from hormone-sensitive disease to castration-resistant disease. In a study using paired prostate-cancer biopsies, membranous B7-H3 was detected in 97% of castration-sensitive samples and 93% of castration-resistant samples.

This apparent persistence makes B7-H3 an attractive target for treatment of advanced disease. A therapy directed against a marker that remains present after metastatic spread and hormonal treatment may have activity across several stages of tumour evolution rather than being limited to a small molecular subgroup. Additional analyses involving thousands of prostate-cancer samples have likewise reported that B7-H3 expression is broadly maintained across disease states, although it varies according to tumour site, hormone-sensitivity status, and other biological factors.

Data about Ris-Rez from the phase 2 ARTEMIS-003 trial were presented in patients with metastatic castration-resistant prostate cancer at ASCO GU 2026. Those results were described as showing encouraging antitumor activity with a generally manageable safety profile. The publicly reported ARTEMIS-003 results said that in taxane-pretreated patients, the confirmed objective response rate was 38.9% and the PSA50 response rate was 40.7%. In taxane-naive patients, the confirmed objective response rate was 50.0% and the PSA50 response rate was 64.0%.

Clinical trial.