Authors
Apostolia M Tsimberidou, Christopher R Cabanski, Alexandra Drakaki, Danny N Khalil, Bilal A Siddiqui, Sreyashi Basu, Kwame Okrah, Diane M Da Silva, Shikha Gautam, Farah A Alayli, Mike Schachter, Justin Fairchild, Wai Chin Foo, Silvia Boffo, Jamie Arnott, Ute Dugan, Sumit K Subudhi, Padmanee Sharma
Published in
Science advances. Volume 12. Issue 42. Pages eaee8730. Oct 16, 2026. Epub Oct 14, 2026.
Abstract
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.
PMID:
42873849
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.
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