PMID- 37651676
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240312
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 41
IP  - 30
DP  - 2023 Oct 20
TI  - Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, 
      Phase III PIVOT IO 001 Trial Results.
PG  - 4756-4767
LID - 10.1200/JCO.23.00172 [doi]
AB  - 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.
FAU - Diab, Adi
AU  - Diab A
AUID- ORCID: 0000-0002-0153-0244
AD  - Melanoma Medical Oncology Department, The University of Texas MD Anderson Cancer 
      Center, Houston, TX.
FAU - Gogas, Helen
AU  - Gogas H
AUID- ORCID: 0000-0002-0451-2885
AD  - First Department of Medicine, National and Kapodistrian University of Athens, 
      Athens, Greece.
FAU - Sandhu, Shahneen
AU  - Sandhu S
AUID- ORCID: 0000-0002-8660-4475
AD  - Department of Medical Oncology, Peter MacCallum Cancer Centre, The University of 
      Melbourne, Melbourne, VIC, Australia.
FAU - Long, Georgina V
AU  - Long GV
AUID- ORCID: 0000-0001-8894-3545
AD  - Melanoma Institute Australia, Royal North Shore and Mater Hospitals, The 
      University of Sydney, Sydney, NSW, Australia.
FAU - Ascierto, Paolo A
AU  - Ascierto PA
AUID- ORCID: 0000-0002-8322-475X
AD  - Melanoma, Cancer Immunotherapy and Development Therapeutics Department, Istituto 
      Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.
FAU - Larkin, James
AU  - Larkin J
AUID- ORCID: 0000-0001-5569-9523
AD  - Medical Oncology, The Royal Marsden Hospital, London, United Kingdom.
FAU - Sznol, Mario
AU  - Sznol M
AUID- ORCID: 0000-0003-4137-9662
AD  - Medical Oncology, Yale Cancer Center, Yale University School of Medicine, Smilow 
      Cancer Hospital Yale New Haven Health, New Haven, CT.
FAU - Franke, Fabio
AU  - Franke F
AD  - Medical Oncology, Oncosite Centro de Pesquisa Clinica, Ijui, Brazil.
FAU - Ciuleanu, Tudor E
AU  - Ciuleanu TE
AD  - Medical Oncology, Institutul Prof Dr Ion Chiricuta, Cluj-Napoca, Romania.
FAU - Pereira, Caio
AU  - Pereira C
AD  - Fundacao Pio XII, Hospital de Cancer de Barretos, Barretos, Brazil.
FAU - Munoz Couselo, Eva
AU  - Munoz Couselo E
AUID- ORCID: 0000-0001-7556-7608
AD  - Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of 
      Oncology (VHIO), Barcelona, Spain.
FAU - Bronzon Damian, Fernanda
AU  - Bronzon Damian F
AUID- ORCID: 0000-0003-4651-3357
AD  - Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil.
FAU - Schenker, Michael
AU  - Schenker M
AUID- ORCID: 0000-0003-2645-6391
AD  - Sf Nectarie Oncology Center, University of Medicine and Pharmacy, Craiova, 
      Romania.
FAU - Perfetti, Aldo
AU  - Perfetti A
AD  - Clinica Adventista Belgrano, Buenos Aires, Argentina.
FAU - Lebbe, Celeste
AU  - Lebbe C
AUID- ORCID: 0000-0002-5854-7290
AD  - AP-HP Department of Dermato-oncology and CIC, INSERM U976, Cancer Institute APHP, 
      Nord-Universite Paris Cite, Universite Paris Cite, Paris, France.
FAU - Quereux, Gaelle
AU  - Quereux G
AD  - Department of Dermatology, CIC 1413, de Cancero-Dermatologie-CIC Biotherapie 
      Nantes, Nantes University Hospital, Nantes, France.
FAU - Meier, Friedegund
AU  - Meier F
AUID- ORCID: 0000-0003-4340-9706
AD  - Skin Cancer Center, National Center for Tumor Diseases, University Cancer Centre 
      Dresden, Dresden, Germany.
AD  - Department of Dermatology, University Hospital Carl Gustav Carus, Dresden, 
      Germany.
FAU - Curti, Brendan D
AU  - Curti BD
AUID- ORCID: 0000-0003-3948-2708
AD  - Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR.
FAU - Rojas, Carlos
AU  - Rojas C
AD  - Medical Oncology, Bradford Hill Clinical Research Center, Santiago, Chile.
FAU - Arriaga, Yull
AU  - Arriaga Y
AD  - Medical Oncology, Bristol Myers Squibb, Princeton, NJ.
FAU - Yang, Haisu
AU  - Yang H
AD  - Medical Oncology, Bristol Myers Squibb, Princeton, NJ.
FAU - Zhou, Ming
AU  - Zhou M
AUID- ORCID: 0000-0003-4101-3185
AD  - Medical Oncology, Bristol Myers Squibb, Princeton, NJ.
FAU - Ravimohan, Shruthi
AU  - Ravimohan S
AD  - Translational Medicine, Bristol Myers Squibb, Princeton, NJ.
FAU - Statkevich, Paul
AU  - Statkevich P
AD  - Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Princeton, NJ.
FAU - Tagliaferri, Mary A
AU  - Tagliaferri MA
AUID- ORCID: 0000-0002-1043-2662
AD  - Clinical Development Department, Nektar Therapeutics, San Francisco, CA.
FAU - Khushalani, Nikhil I
AU  - Khushalani NI
AUID- ORCID: 0000-0002-3636-4143
AD  - Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL.
LA  - eng
SI  - ClinicalTrials.gov/NCT03635983
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230831
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - BNO1JG5MZC (bempegaldesleukin)
RN  - 0 (Ipilimumab)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Humans
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Ipilimumab
MH  - *Melanoma/pathology
MH  - *Nivolumab/therapeutic use
PMC - PMC10602507
COIS- The following represents disclosure information provided by authors of this 
      manuscript. All relationships are considered compensated unless otherwise noted. 
      Relationships are self-held unless noted. I = Immediate Family Member, Inst = My 
      Institution. Relationships may not relate to the subject matter of this 
      manuscript. For more information about ASCO's conflict of interest policy, please 
      refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open 
      Payments is a public database containing information reported by companies about 
      payments made to US-licensed physicians (Open Payments). Nikhil I. Khushalani 
      This author is a member of the Journal of Clinical Oncology Editorial Board. 
      Journal policy recused the author from having any role in the peer review of this 
      manuscript. Stock and Other Ownership Interests: Bellicum Pharmaceuticals, Amarin 
      Corporation, Asensus Surgical Consulting or Advisory Role: Bristol Myers Squibb, 
      AstraZeneca, Regeneron, Array BioPharma, Immunocore, Merck, Incyte, Jounce 
      Therapeutics, Iovance Biotherapeutics, NCCN/Pfizer, Genzyme, Novartis, Nektar, 
      Castle Biosciences, Instil Bio, Replimune Research Funding: Bristol Myers Squibb 
      (Inst), Merck (Inst), Novartis (Inst), GlaxoSmithKline (Inst), HUYA Bioscience 
      International (Inst), Amgen (Inst), Regeneron (Inst), Celgene (Inst), Replimune 
      (Inst), Modulation Therapeutics (Inst) Travel, Accommodations, Expenses: 
      Regeneron Other Relationship: Nektar, Regeneron, Bristol Myers Squibb/Celgene, 
      Replimune No other potential conflicts of interest were reported.
EDAT- 2023/08/31 18:42
MHDA- 2023/10/23 00:42
PMCR- 2023/08/31
CRDT- 2023/08/31 16:04
PHST- 2023/10/23 00:42 [medline]
PHST- 2023/08/31 18:42 [pubmed]
PHST- 2023/08/31 16:04 [entrez]
PHST- 2023/08/31 00:00 [pmc-release]
AID - JCO.23.00172 [pii]
AID - 10.1200/JCO.23.00172 [doi]
PST - ppublish
SO  - J Clin Oncol. 2023 Oct 20;41(30):4756-4767. doi: 10.1200/JCO.23.00172. Epub 2023 
      Aug 31.