European urology oncology · 2026
An Open-label, Phase 1 Dose-finding Study of Single-agent IMU-935, a Novel RORγ/RORγt Inverse Agonist, in Patients with Progressive Metastatic Castration-resistant Prostate Cancer.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Grochot Rafael, Guo Christina, Carreira Suzanne, Crespo Mateus, Welti Jon, Miranda Susana, Figueiredo Ines, Bertan Claudia, Rekowski Jan, Yuan Wei, Tunariu Nina, Abramowicz Katarzyna, Ferreira Ana, Riisnaes Ruth, Neeb Antje, Gurel Bora, Fenor de la Maza Maria de Los Dolores, Chandran Khobe, Carmichael Juliet, Westaby Daniel, Kohlhof Hella, Sharp Adam, Paschalis Alec, de Bono Johann
Аннотация
BACKGROUND AND OBJECTIVE: Retinoic acid receptor-related orphan receptor gamma (RORγ) is frequently overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and, together with retinoic acid-related orphan receptor gamma t (RORγt), can increase androgen receptor (AR) signalling and promote a proinflammatory tumour microenvironment.
METHODS: In this phase 1 dose-finding study (NCT05124795), men with mCRPC received the oral RORγ/RORγt inverse agonist IMU-935 across three dose levels (150 mg, 300 mg, or 450 mg twice daily). The primary objective was to determine the recommended phase 2 dose according to a Bayesian optimal interval design. Key secondary endpoints included evaluation of pharmacokinetics and pharmacodynamics, as well as antitumour activity in terms of prostate-specific antigen (PSA), circulating tumour cells (CTCs), and responses according to Response Evaluation Criteria in Solid Tumours.
KEY FINDINGS AND LIMITATIONS: Eighteen men received IMU-935. No dose-limiting toxicities (DLTs) or any grade (G) ≥3 adverse events (AEs) were reported. The most common treatment-related AEs (TRAEs) were G1 nausea (n = 4; 22%) and G1 vomiting (n = 3; 17%). The only G2 TRAEs observed were anaemia (n = 2; 11%) and gastroesophageal reflux disease (n = 1; 6%). Overall, six men (33%) had a decrease in CTC level from ≥5 to <5 cells/7.5 ml, while one participant whose tumour had mismatch repair deficiency (MMRd) experienced a ≥50% decline in PSA and radiologically stable disease for >6 mo. The median time to PSA progression was 8 wk (range 2-36 wk), and median radiological progression-free survival was 11 wk (range 3.4-36 wk).
CONCLUSIONS AND CLINICAL IMPLICATIONS: IMU-935 was well tolerated with no DLTs. One participant with MMRd mCRPC experienced a PSA response. Overall, however, robust antitumour activity was not observed in this molecularly unselected cohort.
METHODS: In this phase 1 dose-finding study (NCT05124795), men with mCRPC received the oral RORγ/RORγt inverse agonist IMU-935 across three dose levels (150 mg, 300 mg, or 450 mg twice daily). The primary objective was to determine the recommended phase 2 dose according to a Bayesian optimal interval design. Key secondary endpoints included evaluation of pharmacokinetics and pharmacodynamics, as well as antitumour activity in terms of prostate-specific antigen (PSA), circulating tumour cells (CTCs), and responses according to Response Evaluation Criteria in Solid Tumours.
KEY FINDINGS AND LIMITATIONS: Eighteen men received IMU-935. No dose-limiting toxicities (DLTs) or any grade (G) ≥3 adverse events (AEs) were reported. The most common treatment-related AEs (TRAEs) were G1 nausea (n = 4; 22%) and G1 vomiting (n = 3; 17%). The only G2 TRAEs observed were anaemia (n = 2; 11%) and gastroesophageal reflux disease (n = 1; 6%). Overall, six men (33%) had a decrease in CTC level from ≥5 to <5 cells/7.5 ml, while one participant whose tumour had mismatch repair deficiency (MMRd) experienced a ≥50% decline in PSA and radiologically stable disease for >6 mo. The median time to PSA progression was 8 wk (range 2-36 wk), and median radiological progression-free survival was 11 wk (range 3.4-36 wk).
CONCLUSIONS AND CLINICAL IMPLICATIONS: IMU-935 was well tolerated with no DLTs. One participant with MMRd mCRPC experienced a PSA response. Overall, however, robust antitumour activity was not observed in this molecularly unselected cohort.