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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Adi Diab - , University of Texas at Austin (Author)
  • Helen Gogas - , National and Kapodistrian University of Athens (Author)
  • Shahneen Sandhu - , University of Melbourne (Author)
  • Georgina V Long - , University of Sydney (Author)
  • Paolo A Ascierto - , Cancer Immunotherapy and Development Therapeutics Department (Author)
  • James Larkin - , Royal Marsden NHS Foundation Trust (Author)
  • Mario Sznol - , Yale University (Author)
  • Fabio Franke - , Canterbury District Health Board (Author)
  • Tudor E Ciuleanu - , Canterbury District Health Board (Author)
  • Caio Pereira - , Hospital de Câncer de Barretos (Author)
  • Eva Muñoz Couselo - , Vall d'Hebron University Hospital (Author)
  • Fernanda Bronzon Damian - , Hospital São Lucas da PUCRS (Author)
  • Michael Schenker - , Craiova University of Medicine and Pharmacy (Author)
  • Aldo Perfetti - , Clínica Adventista Belgrano (Author)
  • Celeste Lebbe - , Cancer Institute APHP (Author)
  • Gaëlle Quéreux - , CHU de Nantes (Author)
  • Friedegund Meier - , Department of Dermatology, Skin Tumor Center (Author)
  • Brendan D Curti - , Providence Cancer Institute (Author)
  • Carlos Rojas - , Bradford Hill Clinical Research Center (Author)
  • Yull Arriaga - , Canterbury District Health Board (Author)
  • Haisu Yang - , Canterbury District Health Board (Author)
  • Ming Zhou - , Canterbury District Health Board (Author)
  • Shruthi Ravimohan - , Sächsischen Inkubator für Klinische Translation (SIKT) (Author)
  • Paul Statkevich - , Clinical Pharmacology & Pharmacometrics (Author)
  • Mary A Tagliaferri - , TUD Dresden University of Technology (Author)
  • Nikhil I Khushalani - , H. Lee Moffitt Cancer Center & Research Institute (Author)

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.

Details

Original languageEnglish
Pages (from-to)4756-4767
Number of pages12
JournalJournal of Clinical Oncology
Volume41
Issue number30
Publication statusPublished - 20 Oct 2023
Peer-reviewedYes

External IDs

PubMedCentral PMC10602507
Scopus 85174750940
ORCID /0000-0003-4340-9706/work/151982828

Keywords

Keywords

  • Humans, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Ipilimumab, Melanoma/pathology, Nivolumab/therapeutic use