Clinical genitourinary cancer · 2026
Pembrolizumab and Denosumab in Clear-Cell Renal-Cell Carcinoma.
СтатьяМногоцентровое исследованиеКлиническое исследование II 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.
Harris Carole A, Zebic Danka S, Morris Michelle F, Ferguson Tom, Goh Jeffrey C, Martin Andrew J, Underhill Craig, Pook David W, Krieger Laurence, Kichenadasse Ganessan, Joshi Abhishek J, Subramaniam Shalini, Zhang Alison, Joshua Anthony M, Toner Guy C, Vasey Paul A, Prithviraj Prashanth, Stockler Martin R, Davis Ian D, Gedye Craig
Аннотация
BACKGROUND: Anti-PD1 immune checkpoint inhibitors (ICI) are effective in clear-cell renal-cell carcinoma (ccRCC). Preliminary data suggest inhibition of Receptor Activator of Nuclear Factor-κB Ligand (RANKL) signaling may potentiate ICI efficacy. We evaluated the activity and safety of the RANKL-inhibitor denosumab with pembrolizumab in people with pretreated advanced ccRCC.
METHODS: This single-arm, multi-center phase 2 trial enrolled participants with metastatic or unresectable ccRCC progressing on or after VEGFR-targeted tyrosine kinase inhibitor (TKI) therapy. Participants received pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on days 1, 8 and 22, then 3-weekly until disease progression, unacceptable toxicity, or a maximum of 24 months. Primary endpoint was objective tumor response (ORR). Secondary endpoints: median progression free survival (PFS), progression-free survival rate at 6 months (PFS6m), duration of response (DOR), and adverse events (AE).
RESULTS: 59 participants were recruited: male (81%), International Metastatic Database Consortium favorable risk (48%), at least one prior VEGFR-TKI in all participants, 2 or more in 16%. At a median follow-up of 40 months, the ORR was 31% (all partial; 95%CI 20%-45%). Median DOR was 17 months. Median PFS was 7.5 months and PFS6m rate was 53% (95%CI, 39%-65%). Immune-related grade ≥ 3 AEs were reported in 21% of participants; study treatment was discontinued for toxicity in 22%. One participant suffered G3 osteonecrosis of the jaw, and 1 died of myositis attributed to study treatment.
CONCLUSION: The combination of denosumab and pembrolizumab is safe in pretreated clear cell renal carcinoma, with activity meriting further investigation.
METHODS: This single-arm, multi-center phase 2 trial enrolled participants with metastatic or unresectable ccRCC progressing on or after VEGFR-targeted tyrosine kinase inhibitor (TKI) therapy. Participants received pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on days 1, 8 and 22, then 3-weekly until disease progression, unacceptable toxicity, or a maximum of 24 months. Primary endpoint was objective tumor response (ORR). Secondary endpoints: median progression free survival (PFS), progression-free survival rate at 6 months (PFS6m), duration of response (DOR), and adverse events (AE).
RESULTS: 59 participants were recruited: male (81%), International Metastatic Database Consortium favorable risk (48%), at least one prior VEGFR-TKI in all participants, 2 or more in 16%. At a median follow-up of 40 months, the ORR was 31% (all partial; 95%CI 20%-45%). Median DOR was 17 months. Median PFS was 7.5 months and PFS6m rate was 53% (95%CI, 39%-65%). Immune-related grade ≥ 3 AEs were reported in 21% of participants; study treatment was discontinued for toxicity in 22%. One participant suffered G3 osteonecrosis of the jaw, and 1 died of myositis attributed to study treatment.
CONCLUSION: The combination of denosumab and pembrolizumab is safe in pretreated clear cell renal carcinoma, with activity meriting further investigation.