Science advances · 2026
Immune biomarkers of response and resistance to ipilimumab and nivolumab in metastatic castration-resistant prostate cancer.
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Tsimberidou Apostolia M, Cabanski Christopher R, Drakaki Alexandra, Khalil Danny N, Siddiqui Bilal A, Basu Sreyashi, Okrah Kwame, Da Silva Diane M, Gautam Shikha, Alayli Farah A, Schachter Mike, Fairchild Justin, Chin Foo Wai, Boffo Silvia, Arnott Jamie, Dugan Ute, Subudhi Sumit K, Sharma Padmanee
Аннотация
Immune checkpoint therapies have shown limited efficacy in metastatic castration-resistant prostate cancer (mCRPC). The AMADEUS prostate expansion cohort (NCT03651271) evaluated the efficacy, safety, and biomarkers of escalating ipilimumab doses combined with nivolumab. Patients received ipilimumab 1 milligram per kilogram (mg/kg) + nivolumab 360 mg (I1+N360), ipilimumab 3 mg/kg + nivolumab 1 mg/kg (I3+N1), or ipilimumab 5 mg/kg + nivolumab 1 mg/kg (I5+N1). Coprimary endpoints were 6-month disease control rate (DCR) and changes in tumoral CD8 percentage. Thirty-two patients were enrolled. DCRs were 33% (4 of 12) for I1+N360, 20% (1 of 5) for I3+N1, and 20% (3 of 15) for I5+N1. Across cohorts, tumoral CD8 percentage increased by a median of 5.0%. Although higher ipilimumab doses were tolerable, I1+N360 achieved similar disease control and immune activation with a more favorable safety profile. Early disease progression was associated with increased expression of a TREM2-associated myeloid gene signature, which was also significantly enriched in two independent prostate cancer datasets.