Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results

Diab, A; Gogas, H; Sandhu, S; Long, GV; Ascierto, PA; Larkin, J; Sznol, M; Franke, F; Ciuleanu, TE; Pereira, C; Munoz Couselo, E; Bronzon Damian, F; Schenker, M; Perfetti, A; Lebbe, C; Quereux, G; Meier, F; Curti, BD; Rojas, C; Arriaga, Y; Yang, H; Zhou, M; Ravimohan, S; Statkevich, P; Tagliaferri, MA; Khushalani, NI

Author(s): Diab, A; Gogas, H; Sandhu, S; Long, GV; Ascierto, PA; Larkin, J; Sznol, M; Franke, F; Ciuleanu, TE; Pereira, C; Munoz Couselo, E; Bronzon Damian, F; Schenker, M; Perfetti, A; Lebbe, C; Quereux, G; Meier, F; Curti, BD; Rojas, C; Arriaga, Y; Yang, H; Zhou, M; Ravimohan, S; Statkevich, P; Tagliaferri, MA; Khushalani, NI;
Details: Publication Year 2023-10-20,Volume 41,Issue #30,Page 4756-4767
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
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.
Publisher: Lippincott Williams & Wilkins
Keywords: Humans; *Nivolumab/therapeutic use; Ipilimumab; Antineoplastic Combined Chemotherapy Protocols/adverse effects; *Melanoma/pathology
Department(s): Medical Oncology
PubMed ID: 37651676
Publisher's Version: https://doi.org/10.1200/JCO.23.00172
Open Access at Publisher's Site: https://doi.org/10.1200/jco.23.00172
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-10-31 06:07:49

Last Modified: 2023-10-31 06:08:17