Clinical trial NCT04495010: Neoadjuvant Nivolumab+Ipilimumab Followed by Adjuvant Nivolumab or Neoadjuvant Nivolumab+Ipilimumab Followed by Adjuvant Observation Compared With Adjuvant Nivolumab in Treatment-Naive High-risk Melanoma Participants
Official title: A Phase 2, Randomized Study of Neoadjuvant Nivolumab Plus Ipilimumab Followed by Adjuvant Nivolumab or Neoadjuvant Nivolumab Plus Ipilimumab Followed by Either Adjuvant Nivolumab or Postsurgical Observation Depending on Pathologic Response Compared With Adjuvant Nivolumab in Treatment-Naive Patients With Resectable Clinically Detectable Stage III Melanoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2020-07-31
Enrollment: 0
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the role of neoadjuvant immunotherapy and to demonstrate high pathologic complete response (pCR) and near pCR rates in melanoma participants with clinically detectable nodal disease and a high risk of recurrence. Neoadjuvant immunotherapy aims to enhance the systemic T-cell response to tumor antigens while detectable tumor is still present, inducing a stronger and broader tumor-specific immune response. Of the neoadjuvant approaches studied within melanoma, the neoadjuvant combination of nivolumab and ipilimumab has demonstrated high pCR and near pCR rates that may translate to prolonged clinical benefit.


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Males and females, ≥ 12 years of age \[Except: where local regulations and/or institutional policies do not allow for participants \< 18 years of age (adolescent population) to participate. For those sites, the eligible participant population is 18 years of age or local age of majority, inclusive\]
* Diagnosed with cytologically or histologically confirmed Stage IIIB, IIIC, or IIID cutaneous melanoma as per American Joint Committee on Cancer (AJCC) staging system, with ≥ 1 clinically detectable lymph node metastases (N1b, N2b, N3b), which are measurable according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
* Adult participants and adolescents 16 to 18 years old must have an Eastern Cooperative Oncology Group (ECOG) scale performance status of 0 or 1. Adolescents \< 16 years old must have Lanksky Play-Performance Status scale performance of ≥ 60
* Must be treatment-naïve (ie, no prior systemic anticancer therapy as adjuvant therapy for melanoma or unresectable/metastatic melanoma)
* Women and men must agree to follow specific methods of contraception, if applicable, while participating in the trial

Exclusion Criteria:

* Women who are breastfeeding
* Patients with serious or uncontrolled medical disorders
* Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-programmed death-ligand 2 (PD-L2), or anti cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Recurrence-free survival (RFS) Time from Surgery
timeFrame: Up to 5 years
measure: RFS Time from Adjuvant Therapy
timeFrame: Up to 5 years
measure: Pathologic response rate (pRR) by immune-related pathologic response (irPR)
timeFrame: Up to 5 years
measure: Concordance major pathologic response (MPR) by local and central pathology Review
timeFrame: Up to 5 years
measure: RFS by MPR
timeFrame: Up to 5 years
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 5 years
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Up to 5 years
measure: Incidence of deaths
timeFrame: Up to 5 years
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Up to 5 years
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
timeFrame: Up to 5 years
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Up to 5 years
measure: Change from baseline in Health-related quality of life (HRQoL) by the Trial Outcome Index (TOI) and Melanoma Subscale (MS)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Local Institution
state: Arizona
city: Tucson
country: United States
facility: Local Institution
state: Arizona
city: San Francisco
country: United States
facility: Local Institution
state: California
city: Aurora
country: United States
facility: Local Institution
state: Colorado
city: Tampa
country: United States
facility: Local Institution
state: Florida
city: Atlanta
country: United States
facility: Local Institution
state: Georgia
city: Atlanta
country: United States
facility: Local Institution
state: Georgia
city: Marietta
country: United States
facility: Local Institution
state: Georgia
city: Annapolis
country: United States
facility: Local Institution
state: Maryland
city: Boston
country: United States
facility: Local Institution
state: Massachusetts
city: Boston
country: United States
facility: Local Institution
state: Massachusetts
city: Minneapolis
country: United States
facility: Local Institution
state: Minnesota
city: Minneapolis
country: United States
facility: Local Institution
state: Minnesota
city: Hattiesburg
country: United States
facility: Local Institution
state: Mississippi
city: Saint Louis
country: United States
facility: Local Institution
state: Missouri
city: Morristown
country: United States
facility: Local Institution
state: New Jersey
city: New Brunswick
country: United States
facility: Local Institution
state: New Jersey
city: Cleveland
country: United States
facility: Local Institution
state: Ohio
city: Portland
country: United States
facility: Local Institution
state: Oregon
city: Houston
country: United States
facility: Local Institution
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution
state: Utah
city: Charlottesville
country: United States
facility: Local Institution
state: Virginia
city: Seattle
country: United States
facility: Local Institution
state: Washington
city: North Sydney
country: Australia
facility: Local Institution
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution
state: New South Wales
city: Greenslopes
country: Australia
facility: Local Institution
state: Queensland
city: Woolloongabba
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Hobart
country: Australia
facility: Local Institution
state: Tasmania
city: Ballarat
country: Australia
facility: Local Institution
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Doubleview
country: Australia
facility: Local Institution
state: Western Australia
city: Nedlands
country: Australia
facility: Local Institution
state: Western Australia
city: Graz
country: Austria
facility: Local Institution
city: Innsbruck
country: Austria
facility: Local Institution
city: Salzburg
country: Austria
facility: Local Institution
city: St. Poelten
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Brussels
country: Belgium
facility: Local Institution
city: Gent
country: Belgium
facility: Local Institution
city: Wilrijk
country: Belgium
facility: Local Institution
city: Fortaleza
country: Brazil
facility: Local Institution
state: Ceara
city: Brasilia
country: Brazil
facility: Local Institution
state: Distrito Federal
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Porto Alegre
country: Brazil
facility: Local Institution
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution
state: RIO Grande DO SUL
city: Florianopolis
country: Brazil
facility: Local Institution
state: Santa Catarina
city: Sao Jose do Rio Preto
country: Brazil
facility: Local Institution
state: SAO Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Aarhus
country: Denmark
facility: Local Institution
city: Herlev
country: Denmark
facility: Local Institution
city: Odense C
country: Denmark
facility: Local Institution
city: Bordeaux
country: France
facility: Local Institution
city: Dijon
country: France
facility: Local Institution
city: Lille
country: France
facility: Local Institution
city: Marseille
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
city: Nice
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pierre-Benite
country: France
facility: Local Institution
city: Rennes
country: France
facility: Local Institution
city: Sr Priest En Jarez
country: France
facility: Local Institution
city: Toulouse
country: France
facility: Local Institution
city: Villejuif
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Erlangen
country: Germany
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Hannover
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution
city: Kiel
country: Germany
facility: Local Institution
city: Luebeck
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Regensburg
country: Germany
facility: Local Institution
city: Tuebingen
country: Germany
facility: Local Institution
city: Wuerzburg
country: Germany
facility: Local Institution
city: Bergamo
country: Italy
facility: Local Institution
city: Meldola
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Novara
country: Italy
facility: Local Institution
city: Padova
country: Italy
facility: Local Institution
city: Pavia
country: Italy
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Breda
country: Netherlands
facility: Local Institution
city: Geleen
country: Netherlands
facility: Local Institution
city: Leiden
country: Netherlands
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Utrecht
country: Netherlands
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Krasnodar
country: Russian Federation
facility: Local Institution
city: Ryazan
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Haddon Heights
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Malaga
country: Spain
facility: Local Institution
city: Oviedo
country: Spain
facility: Local Institution
city: Santiago de Compostela
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
city: Vaxjo
country: Sweden
facility: Local Institution
city: Zuerich
country: Switzerland
facility: Local Institution
city: Cambridge
country: United Kingdom
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
city: Guildford
country: United Kingdom
facility: Local Institution
city: Leeds
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
city: Manchester
country: United Kingdom
facility: Local Institution
city: Northwood
country: United Kingdom
facility: Local Institution
city: Oxford
country: United Kingdom
facility: Local Institution
city: Sutton
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: