학술논문
Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results.
Document Type
Academic Journal
Author
Diab A; Melanoma Medical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, TX.; Gogas H; First Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; Sandhu S; Department of Medical Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia.; Long GV; Melanoma Institute Australia, Royal North Shore and Mater Hospitals, The University of Sydney, Sydney, NSW, Australia.; Ascierto PA; Melanoma, Cancer Immunotherapy and Development Therapeutics Department, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.; Larkin J; Medical Oncology, The Royal Marsden Hospital, London, United Kingdom.; Sznol M; Medical Oncology, Yale Cancer Center, Yale University School of Medicine, Smilow Cancer Hospital Yale New Haven Health, New Haven, CT.; Franke F; Medical Oncology, Oncosite Centro de Pesquisa Clínica, Ijui, Brazil.; Ciuleanu TE; Medical Oncology, Institutul Prof Dr Ion Chiricuţă, Cluj-Napoca, Romania.; Pereira C; Fundação Pio XII, Hospital de Câncer de Barretos, Barretos, Brazil.; Muñoz Couselo E; Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Bronzon Damian F; Hospital São Lucas da PUCRS, Porto Alegre, Brazil.; Schenker M; Sf Nectarie Oncology Center, University of Medicine and Pharmacy, Craiova, Romania.; Perfetti A; Clínica Adventista Belgrano, Buenos Aires, Argentina.; Lebbe C; AP-HP Department of Dermato-oncology and CIC, INSERM U976, Cancer Institute APHP, Nord-Université Paris Cite, Université Paris Cité, Paris, France.; Quéreux G; Department of Dermatology, CIC 1413, de Cancéro-Dermatologie-CIC Biothérapie Nantes, Nantes University Hospital, Nantes, France.; Meier F; Skin Cancer Center, National Center for Tumor Diseases, University Cancer Centre Dresden, Dresden, Germany.; Department of Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany.; Curti BD; Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR.; Rojas C; Medical Oncology, Bradford Hill Clinical Research Center, Santiago, Chile.; Arriaga Y; Medical Oncology, Bristol Myers Squibb, Princeton, NJ.; Yang H; Medical Oncology, Bristol Myers Squibb, Princeton, NJ.; Zhou M; Medical Oncology, Bristol Myers Squibb, Princeton, NJ.; Ravimohan S; Translational Medicine, Bristol Myers Squibb, Princeton, NJ.; Statkevich P; Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Princeton, NJ.; Tagliaferri MA; Clinical Development Department, Nektar Therapeutics, San Francisco, CA.; Khushalani NI; Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL.
Source
Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Methods: 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.
Results: 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.
Conclusion: 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.