{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:04:53Z","timestamp":1784901893471,"version":"3.55.0"},"reference-count":39,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"unspecified","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health","award":["ZIA BC 010666"],"award-info":[{"award-number":["ZIA BC 010666"]}]},{"name":"Cooperative Research and Development Agreement (CRADA) between the National Cancer Institute and Incyte","award":["CRADA #03142"],"award-info":[{"award-number":["CRADA #03142"]}]},{"name":"Cooperative Research and Development Agreement (CRADA) between the National Cancer Institute EMD Serono Research & Development Institute","award":["CRADA 02666"],"award-info":[{"award-number":["CRADA 02666"]}]},{"name":"Cooperative Research and Development Agreement (CRADA) between the National Cancer Institute and Bavarian Nordic","award":["CRADA 02561"],"award-info":[{"award-number":["CRADA 02561"]}]},{"name":"Cooperative Research and Development Agreement (CRADA) between the NCI and ImmunityBio","award":["CRADA #02997"],"award-info":[{"award-number":["CRADA #02997"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,8]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint blockade is minimally active in unselected castration-resistant prostate cancer (CRPC) and does not reproducibly yield durable decreases in prostate-specific antigen (PSA) levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Quick Efficacy Seeking Trial was designed to employ a combination of agents to initiate an immune response (with BN-Brachyury vaccine), potentiate that response (with nogapendekin-alfa inbakicept (NAI), an interleukin (IL)-15 receptor superagonist), and reduce or eliminate immunosuppressive entities in the tumor microenvironment (with bintrafusp alfa, a dual inhibitor of programmed death-ligand 1 and transforming growth factor beta). Epacadostat (an indoleamine 2,3-dioxygenase (IDO) inhibitor) was also employed in one cohort to reduce immune suppression induced by IDO\u2019s conversion of tryptophan to kynurenine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with CRPC enrolled sequentially to receive vaccine + bintrafusp\u2009alfa (Arm 2.1), vaccine + bintrafusp\u2009alfa + NAI (Arm 2.2), and vaccine + bintrafusp\u2009alfa + NAI + epacadostat (Arm 2.3), with the primary objective to determine response rate. Adverse events in Arms 2.1 and 2.2 were manageable and consistent with the safety profiles of each agent individually, and notable for five individuals developing isolated adrenocorticotropic hormone deficiency. Arm 2.3 was closed early due to skin toxicity. Sustained declines in PSA were seen in 1\/13 (8%) patients in Arm 2.1, 7\/24 (29%) patients in Arm 2.2, including six with proficient mismatch repair\/microsatellite stable tumors, and 0\/6 (0%) patients in Arm 2.3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Analyses of peripheral immune profiles provided evidence of a multifaceted antitumor immune response, including IL-15 receptor superagonist NAI-dependent expansion and activation of natural killer cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, increased effector-to-suppressor immune cell ratios, and induction of cytotoxic immune gene programs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03493945\">NCT03493945<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015336","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:20:20Z","timestamp":1784899220000},"page":"e015336","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Durable responses to triplet immunotherapy targeting TGF-\u03b2, PD-L1, and tumor antigen, with an IL-15 receptor superagonist in mismatch repair proficient castration-resistant prostate 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