{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:08:58Z","timestamp":1780657738231,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pembrolizumab is approved for advanced cutaneous melanoma (aCM). Cabozantinib, an oral multi\u2010tyrosine kinase inhibitor, has demonstrated antitumor activity as monotherapy or in combination with anti\u2010PD\u20101 therapy in malignancies. The objective of this study was to determine the safety and efficacy of cabozantinib and pembrolizumab for patients with aCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase 1b\/2 study enrolled 28 patients with unresectable aCM. In phase 1b, escalating dose levels of cabozantinib (20 mg, 40 mg, and 60 mg) were administered concurrently with pembrolizumab 200 mg intravenously every 3 weeks using a 3\u00a0+\u00a03 design to determine recommended phase 2 dose (RP2D). In phase 2, patients received cabozantinib at RP2D in combination with pembrolizumab using a Simon 2 stage design. Primary end point of phase 2 was overall response rate (ORR). Secondary end points included disease control rate, progression\u2010free survival (PFS), and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Phase 1b enrolled eight patients, cabozantinib 40 mg daily dose level was selected as RP2D. Response rate in stage 1 exceeded predefined criteria for proceeding to expansion phase; however, phase 2 was terminated after 20 patients due to low accrual in the setting of evolving standard of care. Among all treated patients, the most common grade \u22653 toxicities were hypertension (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010, 36%), hypokalemia (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05, 18%), hypophosphatemia (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04, 14%), and ALT elevation (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04, 14%). Among 20 patients treated in phase 2, ORR was 45%, median PFS was 6.6 months, and median OS was 29.5 months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cabozantinib and pembrolizumab combination was explored in treatment\u2010naive aCM. Toxicity was consistent with known profiles, but discontinuation rates were notable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70326","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T16:24:11Z","timestamp":1771345451000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase 1b\/2 study of cabozantinib in combination with pembrolizumab in advanced cutaneous melanoma"],"prefix":"10.1002","volume":"132","author":[{"given":"Yousef","family":"Zakharia","sequence":"first","affiliation":[{"name":"Division of Hematology, Oncology, and Blood and Marrow Transplantation Department of Internal Medicine University of Iowa Health Care  Iowa City Iowa USA"},{"name":"Mayo Clinic Comprehensive Cancer Center  Phoenix Arizona USA"},{"name":"University of Iowa Holden Comprehensive Cancer Center  Iowa City Iowa 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