Radiotherapy and concomitant relugolix (Orgovyx) will be evaluated for the treatment of patients with intermediate-risk prostate cancer in the phase 2 ULTRA-HERO trial (Trial ID: 2024-518388-37-00).1
“Relugolix is an oral, [gonadotropin-releasing hormone agonist] recently tested in a randomized phase 3 trial [NCT03085095] showing reduced risk in terms of cardiovascular events and rapid testosterone recovery [compared with] leuprolide [Lupron],2” Giulio Francolini, MD, a clinical oncologist in the Florence Radiation Oncology Unity at the Azienda Ospedaliero Universitaria Careggi of the University of Florence in Italy, and his coauthors wrote in a poster presentation detailing the study’s design. “Given its rapid testosterone recovery, relugolix may significantly reduce the long-term negative impact of ADT [androgen deprivation therapy] in the specific setting of a short-term duration of treatment.”
This poster was presented during the 2026 Genitourinary Cancers Symposium.
Key Highlights of the Phase 2 ULTRA-HERO Trial
- Radiotherapy and concomitant relugolix will be evaluated for the treatment of patients with intermediate-risk prostate cancer in the phase 2 ULTRA-HERO trial.
- Patients will receive ultrahypofractionated prostate radiotherapy for a total dose of 36.25 Gy in 5 fractions at 7.25 Gy each, every other day in combination with oral relugolix.
- The primary end point is the rate of patients with complete biochemical response (nadir < 0.5 ng/mL) at 6 months after end of radiotherapy.
How is the ULTRA-HERO trial designed?
ULTRA-HERO is a prospective, interventional study that will enroll adult patients with intermediate-risk prostate carcinoma.1,3 Intermediate-risk disease will be defined as a Gleason score of 4+3 and/or at least 50% of biopsy cores being positive and/or at least 2 intermediate risk factors. Patients must also have an International Prostate Symptom Score of less than 15 and a prostate volume of less than 90 cc. Patients with neuroendocrine differentiation, metastatic disease at diagnosis or any high-risk features are excluded from the trial.
Patients will receive ultrahypofractionated prostate radiotherapy for a total dose of 36.25 Gy in 5 fractions at 7.25 Gy each, every other day in combination with oral relugolix. Relugolix will be administered via an attack dose at 360 mg on day 1 followed by a daily dose of 120 mg for 6 months.
The primary end point is the complete biochemical response rate (nadir < 0.5 ng/mL) at 6 months after the end of radiotherapy.1 Study enrollment was initiated in May 2025, and 20 patients were enrolled at the time of the poster presentation.
What prior data have been shared with radiotherapy plus relugolix in prostate cancer?
Findings from the phase 3 study of radiotherapy plus relugolix in men with localized or advanced prostate cancer showed that patients who received short-term ADT with radiotherapy and relugolix (n = 65) experienced an effective 24-week castration rate of 95% (95% CI, 87.1%-99.0%).2 Those treated with long-term ADT plus radiotherapy and relugolix (n = 99) achieved a 48-week sustained castration rate of 96.9% (95% CI, 90.6%-99.0%).
Comparatively, patients who received leuprolide plus long-term ADT and radiotherapy (n = 58) experienced a 48-week sustained castration rate of 96.4% (95% CI, 86.4%-99.1%). Patients in the long-term ADT plus radiotherapy and relugolix group experienced day 4 and day 15 testosterone suppression rates (< 50 ng/dL) of 59.6% and 100%, respectively. These respective rates were 0% and 10.3% in the leuprolide group.
In terms of safety, patients in the short-term ADT group treated with relugolix experienced any-grade hot flash (57%), fatigue (26%), diarrhea (19%), cataracts (15%), nocturia (14%), and pollakiuria (12%). Patients in the long-term ADT group experienced grade 3 or higher hot flash (55%), fatigue (29%), diarrhea (25%), constipation (22%), arthralgia (14%), back pain (14%), dysuria (12%), nocturia (11%), and weight increase (10%).
“Relugolix appears safe, with no new safety concerns reported in patients who received this combination,” the study authors wrote in their conclusion. “Additionally, there appeared to be no difference in time to castration-resistant—free survival between the relugolix and leuprolide acetate cohorts in this radiotherapy subgroup analysis. These results provide evidence of the clinical use of this therapy for patients receiving radiotherapy plus ADT.”
Disclosures: Francolini reported no relevant financial disclosures.
References
- Francolini G, Alongi F, Allegra AG, et al. Ultra-hypofractionated radiotherapy and concomitant oral relugolix for treatment of intermediate risk prostate cancer (ULTRA-HERO). J Clin Oncol. 2026;44(suppl 7):TPS411. doi:10.1200/JCO.2026.44.7_suppl.TPS411
- Spratt DE, George DJ, Shore ND, et al. Efficacy and safety of radiotherapy plus relugolix in men with localized or advanced prostate cancer. JAMA Oncol. 2024;10(5):594-602. doi:10.1001/jamaoncol.2023.7279
- Study on relugolix and radiation therapy for patients with intermediate risk prostate cancer. ClinicalTrials.eu. Updated December 11, 2025. Accessed March 19, 2026. https://clinicaltrials.eu/trial/study-on-relugolix-and-radiation-therapy-for-patients-with-intermediate-risk-prostate-cancer/
