{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:46:48Z","timestamp":1779205608566,"version":"3.51.4"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"name":"Intramural Program of the Center for Cancer Research, National Cancer Institute"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["ZIA BC 010666"],"award-info":[{"award-number":["ZIA BC 010666"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite successes in other malignancies, immune checkpoint blockade (ICB) has not demonstrated reproducible efficacy in mismatch repair-proficient (pMMR) colorectal cancer (CRC). Preclinical studies indicate that multitargeted combination immunotherapy may sensitize resistant tumors to immune-mediated killing. This trial was designed to test this hypothesis by combining agents to induce and augment an immune response in pMMR CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single-center, phase 1\/2 trial, eligible patients had pMMR, RECIST v1.1-measurable metastatic CRC, \u22652 prior lines of therapy, and no prior immunotherapy. The primary endpoint was objective response rate. Patients received triplet therapy: CV-301 (CEA\/MUC-1 vaccine), N-803 (IL-15 receptor superagonist), bintrafusp alfa (bifunctional anti-PD-L1\/TGF\u03b2 \u201ctrap\u201d), or quadruplet therapy (adding PDS01ADC [tumor-targeted IL-12 immunocytokine]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between September 2020 and September 2022, 32 patients enrolled in triplet (n\u2009=\u200912) and quadruplet (n\u2009=\u200920) therapy. The combinations had toxicity profiles consistent with each individual agent included. One complete response durable for 29+ months occurred in a patient with RAS wild-type CRC metastatic to lymph nodes who received quadruplet therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Quadruplet therapy produced one objective response in unselected mCRC patients (n\u2009=\u200920). There were no responses with triplet therapy (n\u2009=\u200912). The role of ICB-based combination immunotherapy in pMMR CRC remains unclear. 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