Efficacy, tolerability, and safety of teverelix DP in patients with advanced prostate cancer: A multicenter, open‐label, phase 2 trial

• Published in: The Prostate Vol. 84; no. 6; pp. 584 - 598
• Main Authors: Ulys, Albertas, Jankevicus, Feliksas, Jievaltas, Mindaugas, Venckus, Raimundas, Auskalnis, Stasys, Kardelis, Zygimantas, Barisiene, Marija, MacLean, Carol M., Os, Steve, Larsen, Finn
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2024
• Subjects: Castration; dose‐finding study; Drug therapy; Erythema; GnRH antagonist; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Injection; Luteinizing hormone; Male; Oligopeptides; phase 2; Pituitary (anterior); Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - surgery; Testosterone; Testosterone - blood; teverelix DP; prostate cancer; dose‐finding study; phase 2; testosterone; teverelix DP; GnRH antagonist
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.24674

Background Teverelix drug product (DP) is a novel injectable gonadotropin‐releasing hormone antagonist. Methods An adaptive phase 2, open‐label, multicenter trial was conducted in patients with advanced prostate cancer to evaluate the efficacy and safety of a combined subcutaneous (SC) and intramuscular (IM) loading dose regimen of teverelix DP of 120 mg SC + 120 mg IM (Group 1; N = 9) or 180 mg SC + 180 mg IM (Group 2; N = 41) administered at a single visit, followed by 6‐weekly SC maintenance doses of 120 mg (Group 1) or 180 mg (Group 2), up to Day 168. The primary endpoint was the proportion of patients achieving castration levels with serum testosterone <0.5 ng/mL at Day 28 with a target castration rate of 90%. Injection sites were inspected by the investigator at every visit and reactions (ISRs) were proactively recorded. Results The target castration rate was reached in Group 2 (97.5%) but not in Group 1 (62.5%). The castration rates were not maintained to Day 42 (Group 2: 82.5%; Group 1: 50.0%). Suppression of testosterone to castrate levels occurred rapidly (median time: 2 days for both groups). Suppression of testosterone, prostate‐specific antigen, follicle‐stimulating hormone, and luteinizing hormone was sustained throughout the treatment period, being more prominent with the higher dose. The adverse event (AE) profile was similar between groups. The most common AEs were injection‐site induration (n = 40: 80.0%), injection‐site erythema (n = 35: 70.0%), and hot flush (n = 21: 42.0%). Most ISRs were Grade 1. Conclusion Overall, the teverelix DP doses were generally well‐tolerated but did not adequately maintain castration levels.