{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:41:33Z","timestamp":1790430093226,"version":"4.1.0"},"reference-count":46,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"26","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,9,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Therapies that produce deep and durable responses in patients with metastatic melanoma are needed. This phase II cohort from the international, single-arm PIVOT-02 study evaluated the CD122-preferential interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) in first-line metastatic melanoma. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> A total of 41 previously untreated patients with stage III\/IV melanoma received BEMPEG 0.006 mg\/kg plus NIVO 360 mg once every 3 weeks for \u2264 2 years; 38 were efficacy-evaluable (\u2265 1 postbaseline scan). Primary end points were safety and objective response rate (blinded independent central review); other end points included progression-free survival, overall survival (OS), and exploratory biomarkers. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> At 29.0 months' median follow-up, the objective response rate was 52.6% (20 of 38 patients), and the complete response rate was 34.2% (13 of 38 patients). Median change in size of target lesions from baseline was \u221278.5% (response-evaluable population); 47.4% (18 of 38 patients) experienced complete clearance of target lesions. Median progression-free survival was 30.9 months (95% CI, 5.3 to not estimable). Median OS was not reached; the 24-month OS rate was 77.0% (95% CI, 60.4 to 87.3). Grade 3 and 4 treatment-related and immune-mediated adverse events occurred in 17.1% (7 of 41) and 4.9% (2 of 41) of patients, respectively. Increased polyfunctional responses in CD8+ and CD4+ T cells were seen in blood after treatment, driven by cytokines with effector functions. Early on-treatment blood biomarkers (CD8+ polyfunctional strength difference and eosinophils) correlated with treatment response. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> BEMPEG in combination with NIVO was tolerated, with relatively low rates of grade 3 and 4 treatment-related and immune-mediated adverse events. The combination had encouraging antitumor activity in first-line metastatic melanoma, including an extended median progression-free survival. Exploratory analyses associated noninvasive, on-treatment biomarkers with response, before radiologic evidence was observed. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.21.00675","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T19:59:29Z","timestamp":1626206369000},"page":"2914-2925","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":82,"title":["Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma"],"prefix":"10.1200","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-0244","authenticated-orcid":false,"given":"Adi","family":"Diab","sequence":"first","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott S.","family":"Tykodi","sequence":"additional","affiliation":[{"name":"University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-8009","authenticated-orcid":false,"given":"Gregory A.","family":"Daniels","sequence":"additional","affiliation":[{"name":"University of California, La Jolla, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-6321","authenticated-orcid":false,"given":"Michele","family":"Maio","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera Universitaria Senese, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan D.","family":"Curti","sequence":"additional","affiliation":[{"name":"Providence Cancer Institute and Earle A. 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