MelanomaPhase 3PIVOT-12NCT04410445
Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence
A Phase 3 study testing Bempegaldesleukin and Nivolumab in people with Melanoma and Melanoma Stage III, run by Nektar Therapeutics at 212 sites in 17 countries.
Trial summary
The main purpose of this study is to compare the efficacy of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA/B/C/D, or Stage IV cutaneous melanoma who are at high risk for recurrence. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Melanoma, Melanoma Stage III, Melanoma Stage IV
- What is being tested?
- Bempegaldesleukin and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 765 participants
- Where
- 212 sitesin 17 countries
- Study dates
- 27 Jul 2020to 22 Sep 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female patients, age 12 years or older at the time of signing the informed consent form (age 18 years or older where local regulations, countries, and/or institutional policies do not allow for patients < 18 years of age (adolescents) to participate). In regions where adolescents are not allowed to participate in the study due to age restrictions, enrolled patients must be ≥ 18 years of age.
- Histologically confirmed Stage IIIA (LN metastasis > 1 mm), IIIB/C/D, or IV (M1a/b/c/d) cutaneous melanoma by AJCC (8th edition) at study entry that has been completely surgically resected within 12 weeks prior to randomization.
- Tumor tissue available from biopsy or resected disease must be provided to central laboratory for PD-L1 status analysis. Must have PD-L1 expression classification for stratification purposes.
- Disease-free status documented by a complete physical examination and imaging studies within 28 days prior to randomization.
Who cannot join
- History of ocular/uveal melanoma or mucosal melanoma.
- Active, known or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy for central nervous system lesions.
- Prior therapy with interferon, talimogene laherparepvec (Imylgic®), interleukin-2 (IL-2) directed therapy, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte-associated protein 4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways).
- Prior malignancy active within the previous 3 years except for locally potentially curable cancers that have been apparently cured.
Trial locations and contacts
212 sites in 17 countries.
212 sites in 17 countries
United States62 sites
Lehigh Valley Physician Group (LVPG) - Hematology Oncology
Allentown, Pennsylvania, 18103
Kaiser Foundation Hospital, Inpatient Pharmacy
Anaheim, California, 92805
Rocky Mountain Cancer Centers (Littleton) - USOR
Aurora, Colorado, 80012
University of Colorado - Cancer Center - PPDS
Aurora, Colorado, 80045
Frontier Cancer Center and Blood Institute
Billings, Montana, 59102
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 32750
University of Virginia Cancer Center
Charlottesville, Virginia, 22903
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, 37404
Rush University Medical Center
Chicago, Illinois, 60612
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Department of Pharmacy Investigational Drug Services
Dallas, Texas, 75235
Texas Oncology (Loop) - USOR
Dallas, Texas, 75246
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Duke Cancer Institute
Durham, North Carolina, 27710
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Kaiser Permanente
Fontana, California, 92335
St. Joseph Heritage Healthcare
Fullerton, California, 92835
Goshen Center For Cancer Care
Goshen, Indiana, 46526
Prisma Health Cancer Institute
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033
MD Anderson Cancer Center
Houston, Texas, 77030
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
University of Kentucky
Lexington, Kentucky, 40536
Banner MD Anderson Cancer Center
Little Rock, Arkansas, 72205
Orlando Health Cancer Institute
Longwood, Florida, 32750
University of Wisconsin
Madison, Wisconsin, 53792
Atlantic Health System
Morristown, New Jersey, 07960
SCRI Tennessee Oncology Nashville
Nashville, Tennessee, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
NYU Langone Medical Center
New York, New York, 10016
Columbia University Medical Center - PIN
New York, New York, 10021
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Nebraska Methodist Hospital
Omaha, Nebraska, 68130
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Hematology Oncology Medical Group of Orange County, Inc.
Orange, California, 92868
University of California Irvine
Orange, California, 92868
Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
H Lee Moffitt Cancer Center and Research Institute
Pittsburgh, Pennsylvania, 15232
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Providence Cancer Institute, Franz Clinic
Portland, Oregon, 97213
Oregon Health and Science University
Portland, Oregon, 97216
Emad Ibrahim, MD, Inc
Redlands, California, 92373
Kaiser Permanente
Riverside, California, 92505
Southern California Permanente Medical Group
Riverside, California, 92505
Blue Ridge Cancer Care - USOR
Roanoke, Virginia, 24014
Mayo Clinic - PIN
Rochester, Minnesota, 55905
Utah Cancer Specialists (Salt Lake City)
Salt Lake City, Utah, 90603
San Francisco Oncology Associates
San Francisco, California, 94115
California Cancer Associates for Research and Excellence
San Marcos, California, 92069
Kaiser Permanente
San Marcos, California, 92078
Angeles Clinic and Research Institute
Santa Monica, California, 90404
John Wayne Cancer Institute
Santa Monica, California, 90404
Honor Health
Scottsdale, Arizona, 85258
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
Northwest Medical Specialties
Tacoma, Washington, 98405
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Germany25 sites
Charité - Universitätsmedizin Berlin
Berlin, 10117
Ruhr Universität Bochum
Bochum, 44791
Elben Klinken Stade - Buxtehude
Buxtehude, 21614
Uniklinik Köln
Cologne, 50937
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 81307
Helios Klinikum Erfurt
Erfurt, 99089
Universitätsklinikum Essen
Essen, 45147
SRH Wald-Klinikum Gera GmbH
Gera, 7548
Universitatsklinikum Halle (Saale)
Halle, 6097
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, 30625
University Clinic Heidelberg
Heidelberg, 69120
SLK Kliniken Heilbronn GmbH
Heilbronn, 74078
Universitatsklinikum Schleswig-Holstein
Kiel, 24105
Universitatsklinikum Leipzig
Leipzig, 04103
Klinikum der Stadt Ludwigshafen gGmbH
Ludwigshafen, 67063
Universitätsklinik Magdeburg
Magdeburg, 39014
Klinikum Mannheim Universitätsklinikum gGmbH
Mannheim, 76297
Universitatsklinikum Munster
Münster, 48149
Fachklinik Hornheide
Münster, 48157
University Clinic Regensburg
Regensburg, 93053
Helios Klinikum Schwerin
Schwerin, 19049
Universitätsklinikum Tübingen
Tübingen, 76297
Universitätsklinikum Ulm
Ulm, 89081
Universitätsklinikum Würzburg
Würzburg, 97080
France16 sites
Centre Hospitalier Universitaire (CHU) Amiens-Picardie - Hopital Sud
Amiens, 80054
CHU Angers
Angers, 49100
Hôpital Saint-André
Bordeau
CHRU de Tours
Chambray-lès-Tours
CHU Estaing
Clermont-Ferrand, 63003
Hôpital Albert Michallon La Tronche
La Tronche, 38043
CHRU Lille
Lille, 59037
Hôtel Dieu - Nantes
Nantes, 44093
CHU de Nice
Nice, 6202
Hôpital Saint Louis
Paris, 75475
Groupe Hospitalier Bichat Claude Bernard
Paris, 75877
Hospices Civils de Lyon
Pierre-Bénite, 69310
EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS
Rennes, 35042
Hôpital Charles Nicolle
Rouen, 76031
Centre Hospitalier Universitaire de Saint Etienne
Saint-Priest-en-Jarez, 42055
Institut Gustave Roussy
Villejuif, 94801
Spain15 sites
Hospital Universitario A Coruña
A Coruña, 15006
Hospital Universitario Germans Trias i Pujol
Badalona, 08911
Hospital de La Santa Creu i Sant Pau
Barcelona, 08025
Hospital Universitari Dexeus - Grupo Quironsalud
Barcelona, 08028
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 08035
ICO l'Hospitalet - Hospital Duran i Reynals
Córdoba, 14004
Hospital Universitario Virgen de La Arrixaca
El Palmar
Hospital Universitario de Jaen
Jaén, 23007
C.H. Regional Reina Sofia - PPDS
L'Hospitalet de Llobregat, 08904
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario HM Sanchinarro - CIOCC
Madrid, 28050
Hospital General Universitario Gregorio Maranon
Madrid, 4628007
Hospital Universitario Virgen de la Victoria
Málaga, 29789
Hospital Universitario Virgen Macarena
Seville, 41009
Consorcio Hospital General Universitario de Valencia
Valencia
Australia13 sites
Royal Adelaide Hospital
Adelaide, 5000
Cairns Hospital
Cairns, 4870
Icon Cancer Care Wesley
Chermside, 4032
Gallipoli Medical Research Foundation
Greenslopes, 4120
Austin Health
Heidelberg, 3084
Alfred Hospital
Melbourne, 3004
Affinity Clinical Research
Nedlands, 6009
Sir Charles Gairdner Hospital
Nedlands, 6009
Melanoma Institute Australia
North Sydney, 2000
Gold Coast University Hospital
Southport, 4215
Tasman Oncology Research
Southport, 4215
Blacktown Hospital
Westmead, 2145
Princess Alexandra Hospital
Woolloongabba, 4102
Italy11 sites
IRCCS Giovanni Paolo II Istituto Oncologico
Bari, 70124
ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII
Bergamo
Fondazione del Piemonte per l'Oncologia (IRCCS)
Candiolo, 10060
Ospedale Policlinico San Martino
Genova
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
Meldola, 47014
Istituto Europeo Di Oncologia
Milan, 20141
Istituto Nazionale Dei Tumori
Milan
Azienda Ospedaliero Universitaria Di Modena Policlinico
Modena, 41100
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
Naples, 80131
Istituto Oncologico Veneto - I.R.C.C.S.
Padova, 35128
Azienda Ospedaliera Universitaria Senese
Siena, 53100
Greece10 sites
Laiko General Hospital of Athens
Ampelokipoi, 11526
Henry Dunant Hospital
Athens, 11526
Metropolitan Hospital - First Oncology Clinic
Athens, 18547
Metropolitan Hospital - Fourth Oncology Clinic
Athens, 18547
Pepagni Hospital
Heraklion, 71110
Medical Center of Athens
Marousi, 15125
Interbalkan Medical Center of Thessaloniki
Pylaia, TK57001
Theageneio Anticancer Oncology Hospital of Thessaloniki
Thessaloniki, 54645
Papageorgiou General Hospital of Thessaloniki
Thessaloniki, 56429
Bioclinic Thessaloniki (Galinos clinic)
Thessaloniki, 86
Russia9 sites
Chelyabinsk Regional Clinical Oncology Dispensary
Chelyabinsk, 454087
Clinical Oncology Centre #1
Krasnodar, 350040
Krasnoyarsk Regional Oncology Center n.a. A.I. Kryzhanovskiy
Krasnoyarsk, 660133
Kursk Regional Oncology Centre
Kursk, 305524
PMI Euromedservice
Pushkin, 196603
Ryazan Regional Clinical Oncology Dispensary
Ryazan, 390011
FSBI National Medical Research Center of Oncology n.a. N.N.Petrov of MHRF
Saint Petersburg, 191758
Railway Clinical Hospital JSC RZhD
Saint Petersburg, 195271
Regional Clinical Oncology Hospital
Yaroslavl, 150040
Netherlands8 sites
VU Medisch Centrum
Amsterdam, 1081HV
Zuyderland Medisch Centrum
Heerlen, 6419
Medisch Centrum Leeuwarden
Leeuwarden, 8934
Leiden University Medical Center
Leiden, 2333ZA
Radboud University Nijmegen Medical Centre
Nijmegen, 6525GA
Universitair Medisch Centrum Utrecht
Utrecht, 3584
Maxima Medisch Centrum
Veldhoven
Isala Klinieken
Zwolle, 8025AB
Czechia7 sites
Mou/Mmci - Ppds
Brno, 65653
Fakultni nemocnice Hradec Kralove
Hradec Králové
Krajska nemocnice Liberec, a.s.
Liberec, 46063
Fakultni nemocnice Olomouc
Olomouc, 79900
Fakultni nemocnice Ostrava
Ostrava Poruba, 70852
Vseobecna Fakultni Nemocnice V Praze
Prague, 12808
Nemocnice Na Bulovce
Prague, 16000
Austria6 sites
Medizinische Universität Graz
Graz, 8036
Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH
Lienz
Landeskrankenhaus Feldkirch
Rankweil, 6830
Salzburger Landeskliniken
Salzburg
Universitätsklinikum St. Pölten
Sankt Pölten, 3100
Allgemeines Krankenhaus der Stadt Wien
Vienna, 1090
Israel6 sites
HaEmek Medical Center
Afula, 18101
Soroka University Medical Centre
Beersheba, 8410501
Rambam Medical Center - PPDS
Haifa, 31096
Hadassah Medical Center - PPDS
Jerusalem, 9574425
Rabin Medical Center - PPDS
Petah Tikva, 49100
Sheba Medical Center - PPDS
Ramat Gan
New Zealand5 sites
Christchurch Hospital
Christchurch, 8140
Dunedin Hospital
Dunedin, 9054
Auckland City Hospital
Heidelberg, 3084
Tauranga Hospital
Tauranga, 3143
Wellington Hospital
Wellington, 6021
Poland5 sites
Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku
Bialystok, 15-027
Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
Bydgoszcz, 85796
Uniwersyteckie Centrum Kliniczne
Gdansk, 80952
NZOZ NEUROMED M. I M. Nastaj Spolka Partnerska
Lublin, 20064
Szpital Kliniczny im. Heliodora Swiecickiego w Poznaniu
Poznan, 60780
Portugal5 sites
Centro Hospitalar E Universitário de Coimbra EPE
Coimbra, 3004-561
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
Lisbon, 1099-023
Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, 1649-035
Hospital CUF Tejo
Lisbon, 1649-035
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
Porto, 4200-072
United Kingdom5 sites
Addenbrooke's Hospital
Cambridge, CB20QQ
Castle Hill Hospital
Cottingham, HU165JQ
Leicester Royal Infirmary
Leicester, LE15WW
Nottingham City Hospital
Nottingham, BG72UH
Royal Cornwall Hospital
Truro, TR13LJ
Romania4 sites
Affidea Romania SRL
Bucharest, 022328
S.C. Medisprof SRL
Cluj-Napoca, 400641
S.C. Onco Clinic Consult SA
Craiova, 200094
Oncology Center Sfantul Nectarie
Craiova, 200347
About this study
Official title: A Phase 3, Randomized, Open-label Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence (PIVOT-12)
The main purpose of this study is to compare the efficacy of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA/B/C/D, or Stage IV cutaneous melanoma who are at high risk for recurrence.
Read the detailed description
The main purpose of this study is to compare the efficacy, as measured by recurrence-free survival (RFS) by blinded independent central review (BICR), of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (lymph node [LN] metastasis > 1 mm), Stage IIIB/C/D, or Stage IV (American Joint Committee on Cancer [AJCC] 8th edition) cutaneous melanoma with no evidence of disease (NED) who are at high risk for recurrence.
- Conditions
- Melanoma, Melanoma Stage III, Melanoma Stage IV, Melanoma (Skin)
- Being tested
- Bempegaldesleukin, Nivolumab
- Keywords
- CD122-Biased Agonist, CD122-Biased Cytokine, IL-2 Receptor Agonist, NKTR-214, Bempegaldesleukin, IL-2, Immunotherapy, BEMPEG, Nivolumab, Opdivo®, NIVO, Adjuvant, Skin Cancer, Resectable Melanoma, High Risk of Recurrence Melanoma, Post Resection, Checkpoint Inhibitor
- Medical subject headings
- Melanoma, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BempegaldesleukinBiological
Also called NKTR-214, BMS-986321
Specified dose on specified days
NivolumabBiological
Also called Opdivo®, BMS-936558
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Combination of bempegaldesleukin (NKTR-214) + nivolumab | Experimental | Arm A: Participants will receive bempegaldesleukin (NKTR-214) IV in combination with nivolumab every 3 weeks. Receives: Biological: Bempegaldesleukin; Biological: Nivolumab |
| Nivolumab | Active comparator | Arm B: Participants will receive nivolumab IV alone every 4 weeks. Receives: Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free Survival (RFS) by Blinded Independent Central Review (BICR) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.
Recurrence-free Survival (RFS) of bempegaldesleukin plus nivolumab versus nivolumab alone is determined based on the disease recurrence date provided by Blinded Independent Central Review (BICR) and is defined as the time between date of randomization and date of first recurrence (local, regional, or distant metastasis by BICR), new primary melanoma (by BICR), or all-cause death, whichever occurs first.
Measured: Up to 21 months
Secondary outcomes (8)
Overall Survival (OS) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone
Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. Patients who do not have a date of death will be censored on the last date for which a patient was known to be alive.
Measured: Up to 21 months
Distant Metastasis-Free Survival (DMFS) by Investigator in Patients Who Are Stage III at Study Entry.
Distant metastasis-free survival (DMFS) by Investigator is defined as the time between the date of randomization and the date of first distant metastasis by Investigator or date of death due to any cause, in patients who have Stage III melanoma at study entry.
Measured: Up to 21 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
To evaluate safety and tolerability of (NKTR-214) 0.006 mg/kg in combination with nivolumab 360 mg IV infusion (or 4.5 mg/kg IV infusion q3w for patients <40 kg) and nivolumab 480 mg IV infusion (or 6.0 mg/kg IV infusion q4w for patients < 40 kg). Treatment-emergent adverse event (TEAE) is defined as an AE that was not present prior to treatment with study drug but appeared following treatment or was present at treatment start date but worsened during treatment-emergent period. The treatment-emergent period is defined as the period from the date of the first dose of study drug up to 30 days after the date of the last dose of study drug or the day prior to the initiation of subsequent anticancer treatment, whichever occurs first.
Measured: Approximately up to 21 months
Changes at 6 Months of Treatment From Baseline in Scores for the Global Health/Quality of Life (GH/QoL) and Physical Functioning Subscales of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire
The EORTC QLQ-C30 comprises 30 items (i.e. single questions). 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the global health status/quality of life scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. Due to the study termination, results for the mean change from baseline for GH/QoL and the physical functioning subscale were analyzed at approximately 6 months of treatment.
Measured: From baseline, up to approximately 6 months
Programmed Death-Ligand 1 (PD-L1) Expression as a Predictive Biomarker for Recurrence-free Survival (RFS)
The predictive strength of Programmed Death-Ligand 1 (PD-L1) expression as a biomarker will be measured by the endpoint RFS by BICR based on PD-L1 expression level.
Measured: Up to 21 months
Recurrence-free Survival (RFS) by Investigator of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.
Recurrence-free Survival by Investigator is defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis by Investigator), new primary melanoma (by Investigator), or all-cause death, whichever occurs first.
Measured: Up to 21 months
Time to Disease Progression After the Next Line of Treatment for Study Patients Following Discontinuation of Bempegaldesleukin Plus Nivolumab Versus Nivolumab
Time to disease progression after the next line of treatment is defined as time from randomization to progression per Investigator after the start of next line of therapy or death, whichever occurs first. Patients who were alive and without progression after the next line of therapy can be censored at last known alive date.
Measured: Up to 21 months
Distant Metastasis-Free Survival (DMFS) by Blinded Independent Central Review (BICR) in Patients Who Are Stage III at Study Entry.
Distant Metastasis-Free Survival (DMFS) by Blinded Independent Central Review (BICR) is defined as the time between the date of randomization and the date of first distant metastasis by BICR or date of death due to any cause, whichever occurs first, in patients who have Stage III melanoma at study entry.
Measured: Up to 21 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2020
- Study start27 Jul 2020
- Primary completion22 Sep 2022
- Study completion22 Sep 2022
Why it stopped: (Sponsor decision)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized in a 1:1 ratio to one of two treatment arms
- Masking
- None (open label)
- Enrolment
- 765 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nektar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Nektar Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04410445
- Sponsor's protocol ID
- 20-214-29/CA045-022
- Acronym
- PIVOT-12
- Status last verified
- Mar 2023
- First submitted
- 27 May 2020
- Last updated
- 21 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Eggermont AM, Ascierto PA, Khushalani NI, Schadendorf D, Boland G, Weber J, Lewis KD, Johnson D, Rivalland G, Khattak A, Majem M, Gogas H, Long GV, Currie SL, Chien D, Tagliaferri MA, Carlino MS, Diab A. PIVOT-12: a phase III study of adjuvant bempegaldesleukin plus nivolumab in resected stage III/IV melanoma at high risk for recurrence. Future Oncol. 2022 Mar;18(8):903-913. doi: 10.2217/fon-2021-1286. Epub 2022 Jan 25.
PubMed 35073733
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Open-label Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence (PIVOT-12)
- ClinicalTrials.gov ID
- NCT04410445
- Acronym / sponsor ID
- PIVOT-12 / 20-214-29/CA045-022
- Conditions
- Melanoma, Melanoma Stage III, Melanoma Stage IV, Melanoma (Skin)
- Keywords
- CD122-Biased Agonist, CD122-Biased Cytokine, IL-2 Receptor Agonist, NKTR-214, Bempegaldesleukin, IL-2, Immunotherapy, BEMPEG
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: (Sponsor decision)
- Enrolment
- 765 participants (actual)
- Lead sponsor
- Nektar TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 27 Jul 2020 (actual)
- Primary completion
- 22 Sep 2022 (actual)
- Study completion
- 22 Sep 2022 (actual)
- First posted
- 1 Jun 2020 (actual)
- Results
- Posted 21 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to compare the efficacy of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA/B/C/D, or Stage IV cutaneous melanoma who are at high risk for recurrence.
Detailed description
The main purpose of this study is to compare the efficacy, as measured by recurrence-free survival (RFS) by blinded independent central review (BICR), of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (lymph node [LN] metastasis > 1 mm), Stage IIIB/C/D, or Stage IV (American Joint Committee on Cancer [AJCC] 8th edition) cutaneous melanoma with no evidence of disease (NED) who are at high risk for recurrence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomized in a 1:1 ratio to one of two treatment arms
| Arm | Type | Receives |
|---|---|---|
| Combination of bempegaldesleukin (NKTR-214) + nivolumab | Experimental | Biological: Bempegaldesleukin, Biological: NivolumabArm A: Participants will receive bempegaldesleukin (NKTR-214) IV in combination with nivolumab every 3 weeks. |
| Nivolumab | Active comparator | Biological: NivolumabArm B: Participants will receive nivolumab IV alone every 4 weeks. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female patients, age 12 years or older at the time of signing the informed consent form (age 18 years or older where local regulations, countries, and/or institutional policies do not allow for patients < 18 years of age (adolescents) to participate). In regions where adolescents are not allowed to participate in the study due to age restrictions, enrolled patients must be ≥ 18 years of age.
- Histologically confirmed Stage IIIA (LN metastasis > 1 mm), IIIB/C/D, or IV (M1a/b/c/d) cutaneous melanoma by AJCC (8th edition) at study entry that has been completely surgically resected within 12 weeks prior to randomization.
- Tumor tissue available from biopsy or resected disease must be provided to central laboratory for PD-L1 status analysis. Must have PD-L1 expression classification for stratification purposes.
- Disease-free status documented by a complete physical examination and imaging studies within 28 days prior to randomization.
Key exclusion criteria (6 listed)
- History of ocular/uveal melanoma or mucosal melanoma.
- Active, known or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy for central nervous system lesions.
- Prior therapy with interferon, talimogene laherparepvec (Imylgic®), interleukin-2 (IL-2) directed therapy, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte-associated protein 4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BempegaldesleukinAlso: NKTR-214, BMS-986321Specified dose on specified days | Biological | Combination of bempegaldesleukin (NKTR-214) + nivolumab |
| NivolumabAlso: Opdivo®, BMS-936558Specified dose on specified days | Biological | Combination of bempegaldesleukin (NKTR-214) + nivolumab, Nivolumab |
Primary outcome
Recurrence-free Survival (RFS) by Blinded Independent Central Review (BICR) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.
Time frame: Up to 21 months
Recurrence-free Survival (RFS) of bempegaldesleukin plus nivolumab versus nivolumab alone is determined based on the disease recurrence date provided by Blinded Independent Central Review (BICR) and is defined as the time between date of randomization and date of first recurrence (local, regional, or distant metastasis by BICR), new primary melanoma (by BICR), or all-cause death, whichever occurs first.
8 secondary outcomes
Overall Survival (OS) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone
Time frame: Up to 21 months
Distant Metastasis-Free Survival (DMFS) by Investigator in Patients Who Are Stage III at Study Entry.
Time frame: Up to 21 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Approximately up to 21 months
Changes at 6 Months of Treatment From Baseline in Scores for the Global Health/Quality of Life (GH/QoL) and Physical Functioning Subscales of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire
Time frame: From baseline, up to approximately 6 months
Programmed Death-Ligand 1 (PD-L1) Expression as a Predictive Biomarker for Recurrence-free Survival (RFS)
Time frame: Up to 21 months
Recurrence-free Survival (RFS) by Investigator of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.
Time frame: Up to 21 months
Time to Disease Progression After the Next Line of Treatment for Study Patients Following Discontinuation of Bempegaldesleukin Plus Nivolumab Versus Nivolumab
Time frame: Up to 21 months
Distant Metastasis-Free Survival (DMFS) by Blinded Independent Central Review (BICR) in Patients Who Are Stage III at Study Entry.
Time frame: Up to 21 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35073733Eggermont AM, Ascierto PA, Khushalani NI, Schadendorf D, Boland G, Weber J, Lewis KD, Johnson D, Rivalland G, Khattak A, Majem M, Gogas H, Long GV, Currie SL, Chien D, Tagliaferri MA, Carlino MS, Diab A. PIVOT-12: a phase III study of adjuvant bempegaldesleukin plus nivolumab in resected stage III/IV melanoma at high risk for recurrence. Future Oncol. 2022 Mar;18(8):903-913. doi: 10.2217/fon-2021-1286. Epub 2022 Jan 25.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Nektar Therapeutics
212 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bempegaldesleukin and Nivolumab in people with Melanoma and Melanoma Stage III, run by Nektar Therapeutics at 212 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 212 sites in United States, Germany, France, Spain, Australia and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence-free Survival (RFS) by Blinded Independent Central Review (BICR) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone. (time frame: Up to 21 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04410445, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2023.