{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:25:55Z","timestamp":1792553155564,"version":"4.5.0"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Efficacy of immune checkpoint inhibitors in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) is limited. The NEPTUNES study evaluated combination nivolumab and ipilimumab in patients with immunogenic signature\u2013positive (ImS+) mCRPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>This open-label, 2-cohort, phase II trial enrolled patients with ImS+ mCRPC progressing on \u22651 previous line of treatment. ImS+ was defined by (1) mismatch repair deficiency (MMRD); (2) DNA damage repair gene loss; and\/or (3) high inflammatory infiltrate (HII). Patients received four doses of nivolumab 1 mg\/kg + ipilimumab 3 mg\/kg (C1) or nivolumab 3 mg\/kg + ipilimumab 1 mg\/kg (C2) followed by nivolumab 480 mg once every 4 weeks up to 10 cycles. The primary end point was composite response rate (CRR) assessed radiologically, biochemically, and by reduction of circulating tumor cells. Secondary end points included toxicity, progression-free survival, overall survival, and duration of response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Between May 2018 and June 2022, 35 (C1) and 36 (C2) patients commenced treatment. The CRR in C1 was 14\/35 (40%, 90% CI, 26% to 55%) and in C2 was 9\/36 (25%, 90% CI, 14% to 40%). The overall CRR was 23\/71 (32%, 90% CI, 23% to 43%). Response rates were higher in patients with MMRD (7\/10), BRCA2 loss (4\/8), and HII \u00b1 other ImS+ features (13\/30). Duration of response for patients with HII without other ImS+ features, DNA repair gene loss without MMRD, and MMRD was 2.6, 17.3, and 10 months, respectively. Grade 3 to 4 treatment-related adverse events occurred in 22\/35 (63%) in C1 and 12\/36 (33%) patients in C2. There were no treatment-related deaths.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Nivolumab 1 mg\/kg + ipilimumab 3 mg\/kg is an active treatment in ImS+ pretreated mCRPC. Nivolumab 3 mg\/kg + ipilimumab 1 mg\/kg has less toxicity but may have lower efficacy. HII is a promising prospectively tested predictive biomarker in prostate cancer that could be integrated into future trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-24-02637","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T19:59:10Z","timestamp":1753732750000},"page":"3070-3080","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Nivolumab and Ipilimumab for Metastatic Castration-Resistant Prostate Cancer With an Immunogenic Signature: The Multicenter, Two-Cohort, Phase II NEPTUNES Study"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-0115","authenticated-orcid":true,"given":"Gianmarco","family":"Leone","sequence":"first","affiliation":[{"name":"University College London Cancer Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yien Ning 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