{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:57:14Z","timestamp":1792112234072,"version":"4.4.0"},"reference-count":23,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"30","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,10,20]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983 ) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> Patients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> In 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.23.00172","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T20:01:13Z","timestamp":1693512073000},"page":"4756-4767","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":87,"title":["Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results"],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct03635983","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-0244","authenticated-orcid":false,"given":"Adi","family":"Diab","sequence":"first","affiliation":[{"name":"Melanoma Medical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-2885","authenticated-orcid":false,"given":"Helen","family":"Gogas","sequence":"additional","affiliation":[{"name":"First Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8660-4475","authenticated-orcid":false,"given":"Shahneen","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-3545","authenticated-orcid":false,"given":"Georgina V.","family":"Long","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, Royal North Shore and Mater Hospitals, The University of Sydney, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo A.","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Department, Istituto Nazionale Tumori IRCCS Fondazione G. 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