Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence

Melanoma Clinical Trial

— PIVOT-12  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04410445
• Other study ID #: 20-214-29/CA045-022
• Status: Terminated
• Phase: Phase 3
• Start date: July 27, 2020
• Est. completion date: September 22, 2022

Study information

• Verified date: March 2023
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 765
• Est. completion date: September 22, 2022
• Est. primary completion date: September 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)
• Melanoma Stage III
• Melanoma Stage IV
• Recurrence

Intervention

Biological:
• Bempegaldesleukin
Specified dose on specified days
• Nivolumab
Specified dose on specified days

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Cairns Hospital	Cairns
Australia	Icon Cancer Care Wesley	Chermside
Australia	Gallipoli Medical Research Foundation	Greenslopes
Australia	Austin Health	Heidelberg
Australia	Alfred Hospital	Melbourne
Australia	Affinity Clinical Research	Nedlands
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Melanoma Institute Australia	North Sydney
Australia	Gold Coast University Hospital	Southport
Australia	Tasman Oncology Research	Southport
Australia	Blacktown Hospital	Westmead
Australia	Princess Alexandra Hospital	Woolloongabba
Austria	Medizinische Universität Graz	Graz
Austria	Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH	Lienz
Austria	Landeskrankenhaus Feldkirch	Rankweil
Austria	Salzburger Landeskliniken	Salzburg
Austria	Universitätsklinikum St. Pölten	St.Pölten
Austria	Allgemeines Krankenhaus der Stadt Wien	Vienna
Czechia	Mou/Mmci - Ppds	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Krajska nemocnice Liberec, a.s.	Liberec
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava Poruba
Czechia	Nemocnice Na Bulovce	Prague
Czechia	Vseobecna Fakultni Nemocnice V Praze	Praha
France	Centre Hospitalier Universitaire (CHU) Amiens-Picardie - Hopital Sud	Amiens
France	CHU Angers	Angers
France	Hôpital Saint-André	Bordeau
France	CHRU de Tours	Chambray-lès-Tours
France	CHU Estaing	Clermont-Ferrand
France	Hôpital Albert Michallon La Tronche	La Tronche
France	CHRU Lille	Lille
France	Hôtel Dieu - Nantes	Nantes
France	CHU de Nice	Nice
France	Groupe Hospitalier Bichat Claude Bernard	Paris
France	Hôpital Saint Louis	Paris
France	Hospices Civils de Lyon	Pierre-Bénite
France	EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS	Rennes
France	Hôpital Charles Nicolle	Rouen
France	Centre Hospitalier Universitaire de Saint Etienne	Saint-Priest-en-Jarez
France	Institut Gustave Roussy	Villejuif
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Ruhr Universität Bochum	Bochum
Germany	Elben Klinken Stade - Buxtehude	Buxtehude
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Universitätsklinikum Essen	Essen
Germany	SRH Wald-Klinikum Gera GmbH	Gera
Germany	Universitatsklinikum Halle (Saale)	Halle
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	University Clinic Heidelberg	Heidelberg
Germany	SLK Kliniken Heilbronn GmbH	Heilbronn
Germany	Universitatsklinikum Schleswig-Holstein	Kiel
Germany	Uniklinik Köln	Köln
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Klinikum der Stadt Ludwigshafen gGmbH	Ludwigshafen
Germany	Universitätsklinik Magdeburg	Magdeburg
Germany	Klinikum Mannheim Universitätsklinikum gGmbH	Mannheim
Germany	Fachklinik Hornheide	Münster
Germany	Universitatsklinikum Munster	Münster
Germany	University Clinic Regensburg	Regensburg
Germany	Helios Klinikum Schwerin	Schwerin
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitätsklinikum Ulm	Ulm
Germany	Universitätsklinikum Würzburg	Würzburg
Greece	Laiko General Hospital of Athens	Ampelokipoi
Greece	Henry Dunant Hospital	Athens
Greece	Metropolitan Hospital - First Oncology Clinic	Athens
Greece	Metropolitan Hospital - Fourth Oncology Clinic	Athens
Greece	Pepagni Hospital	Heraklion
Greece	Medical Center of Athens	Maroúsi
Greece	Interbalkan Medical Center of Thessaloniki	Pylaía
Greece	Bioclinic Thessaloniki (Galinos clinic)	Thessaloníki
Greece	Papageorgiou General Hospital of Thessaloniki	Thessaloníki
Greece	Theageneio Anticancer Oncology Hospital of Thessaloniki	Thessaloníki
Israel	HaEmek Medical Center	Afula
Israel	Soroka University Medical Centre	Be'er Sheva
Israel	Rambam Medical Center - PPDS	Haifa
Israel	Hadassah Medical Center - PPDS	Jerusalem
Israel	Rabin Medical Center - PPDS	Petah tikva
Israel	Sheba Medical Center - PPDS	Ramat Gan
Italy	IRCCS Giovanni Paolo II Istituto Oncologico	Bari
Italy	ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Fondazione del Piemonte per l'Oncologia (IRCCS)	Candiolo
Italy	Ospedale Policlinico San Martino	Genova
Italy	Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS	Meldola
Italy	Istituto Europeo Di Oncologia	Milano
Italy	Istituto Nazionale Dei Tumori	Milano
Italy	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena
Italy	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale	Napoli
Italy	Istituto Oncologico Veneto - I.R.C.C.S.	Padova
Italy	Azienda Ospedaliera Universitaria Senese	Siena
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Netherlands	Maxima Medisch Centrum	Veldhoven
Netherlands	Isala Klinieken	Zwolle
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Auckland City Hospital	Heidelberg
New Zealand	Tauranga Hospital	Tauranga
New Zealand	Wellington Hospital	Wellington
Poland	Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku	Bialystok
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	NZOZ NEUROMED M. I M. Nastaj Spolka Partnerska	Lublin
Poland	Szpital Kliniczny im. Heliodora Swiecickiego w Poznaniu	Poznan
Portugal	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra
Portugal	Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria	Lisboa
Portugal	Hospital CUF Tejo	Lisboa
Portugal	Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.	Lisbon
Portugal	Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS	Porto
Romania	Affidea Romania SRL	Bucharest
Romania	S.C. Medisprof SRL	Cluj-Napoca
Romania	Oncology Center Sfantul Nectarie	Craiova
Romania	S.C. Onco Clinic Consult SA	Craiova
Russian Federation	Chelyabinsk Regional Clinical Oncology Dispensary	Chelyabinsk
Russian Federation	Clinical Oncology Centre #1	Krasnodar
Russian Federation	Krasnoyarsk Regional Oncology Center n.a. A.I. Kryzhanovskiy	Krasnoyarsk
Russian Federation	Kursk Regional Oncology Centre	Kursk
Russian Federation	PMI Euromedservice	Pushkin
Russian Federation	Ryazan Regional Clinical Oncology Dispensary	Ryazan'
Russian Federation	FSBI National Medical Research Center of Oncology n.a. N.N.Petrov of MHRF	Saint Petersburg
Russian Federation	Railway Clinical Hospital JSC RZhD	Saint Petersburg
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl
Spain	Hospital Universitario A Coruña	A Coruña
Spain	Hospital Universitario Germans Trias i Pujol	Badalona
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Dexeus - Grupo Quironsalud	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	Córdoba
Spain	Hospital Universitario Virgen de La Arrixaca	El Palmar
Spain	Hospital Universitario de Jaen	Jaén
Spain	C.H. Regional Reina Sofia - PPDS	L'Hospitalet De Llobregat
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro - CIOCC	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Royal Cornwall Hospital	Truro
United States	Lehigh Valley Physician Group (LVPG) - Hematology Oncology	Allentown	Pennsylvania
United States	Kaiser Foundation Hospital, Inpatient Pharmacy	Anaheim	California
United States	Rocky Mountain Cancer Centers (Littleton) - USOR	Aurora	Colorado
United States	University of Colorado - Cancer Center - PPDS	Aurora	Colorado
United States	Frontier Cancer Center and Blood Institute	Billings	Montana
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Department of Pharmacy Investigational Drug Services	Dallas	Texas
United States	Texas Oncology (Loop) - USOR	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke Cancer Institute	Durham	North Carolina
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Kaiser Permanente	Fontana	California
United States	St. Joseph Heritage Healthcare	Fullerton	California
United States	Goshen Center For Cancer Care	Goshen	Indiana
United States	Prisma Health Cancer Institute	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	University of Kentucky	Lexington	Kentucky
United States	Banner MD Anderson Cancer Center	Little Rock	Arkansas
United States	Orlando Health Cancer Institute	Longwood	Florida
United States	University of Wisconsin	Madison	Wisconsin
United States	Atlantic Health System	Morristown	New Jersey
United States	SCRI Tennessee Oncology Nashville	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center - PIN	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Hematology Oncology Medical Group of Orange County, Inc.	Orange	California
United States	University of California Irvine	Orange	California
United States	Jefferson University Hospital	Philadelphia	Pennsylvania
United States	H Lee Moffitt Cancer Center and Research Institute	Pittsburgh	Pennsylvania
United States	Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Cancer Institute, Franz Clinic	Portland	Oregon
United States	Emad Ibrahim, MD, Inc	Redlands	California
United States	Kaiser Permanente	Riverside	California
United States	Southern California Permanente Medical Group	Riverside	California
United States	Blue Ridge Cancer Care - USOR	Roanoke	Virginia
United States	Mayo Clinic - PIN	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Utah Cancer Specialists (Salt Lake City)	Salt Lake City	Utah
United States	San Francisco Oncology Associates	San Francisco	California
United States	California Cancer Associates for Research and Excellence	San Marcos	California
United States	Kaiser Permanente	San Marcos	California
United States	Angeles Clinic and Research Institute	Santa Monica	California
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Honor Health	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Northwest Medical Specialties	Tacoma	Washington
United States	MedStar Georgetown University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Nektar Therapeutics	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Netherlands,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 21 months
Secondary	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.	Up to 21 months
Secondary	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.	Up to 21 months
Secondary	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.	Approximately up to 21 months
Secondary	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.	From baseline, up to approximately 6 months
Secondary	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.	Up to 21 months
Secondary	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.	Up to 21 months
Secondary	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.	Up to 21 months
Secondary	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.	Up to 21 months