Clinical trial NCT03668119: A Study of Nivolumab Combined With Ipilimumab and Nivolumab Alone in Patients With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)
Official title: A Randomized, Open-Label, Phase 2 Study of Nivolumab in Combination With Ipilimumab or Nivolumab Monotherapy in Participants With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pan Tumor
Keywords: TMB-H
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2018-09-12
Enrollment: 212
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 demonstrate the clinical activity of nivolumab in combination with ipilimumab in multiple types of tumors based on their Tumor Mutational Burden status.


Eligibility criteria: Inclusion Criteria:

* Participants with a refractory, metastatic, or unresectable histologically or cytologically confirmed solid malignant tumor with high tumor mutational burden (TMB-H) who are refractory to standard local therapies, or for which no standard treatment is available.
* Must be able to provide tissue and blood TMB-H testing results
* Must have measurable disease for response assessment

Exclusion Criteria:

* Participants with melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or hematological malignancy as primary site of disease
* Participants who received prior treatment with an anti-programmed death-1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), anti-programmed death ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
* Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment

Other protocol defined inclusion/exclusion criteria apply.

Primary outcomes:
measure: Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A
timeFrame: From date of randomization up to 42 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm B
timeFrame: From date of randomization up to 57 months
measure: Objective Response Rate (ORR) Per Investigator
timeFrame: From date of randomization up to 57 months
measure: Duration of Response (DoR) Per Investigator
timeFrame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
measure: Duration of Response (DoR) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
measure: Time to Objective Response (TTR) Per Investigator
timeFrame: From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months)
measure: Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months)
measure: Clinical Benefit Rate (CBR) Per Investigator
timeFrame: From date of randomization up to 57 months
measure: Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization up to 57 months
measure: Progression Free Survival (PFS) Per Investigator
timeFrame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
measure: Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
measure: Overall Survival (OS)
timeFrame: From date of randomization to date of death (Up to 57 months)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose to 30 days post last dose (Up to 25 months)
measure: Number of Participants With On-Treatment Laboratory Parameters
timeFrame: From first dose to 30 days post last dose (Up to 25 months)
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: John Wayne Cancer Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Minneapolis
country: United States
facility: Local Institution - 0093
state: Minnesota
city: Johnson City
country: United States
facility: Broome Oncology
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Portland
country: United States
facility: Local Institution - 0079
state: Oregon
city: Austin
country: United States
facility: Local Institution - 0095
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0094
state: Texas
city: Houston
country: United States
facility: Local Institution - 0090
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Ciudad Autonoma Beunos Aires
country: Argentina
facility: Local Institution - 0016
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Local Institution - 0087
state: Buenos Aires
city: Caba
country: Argentina
facility: Local Institution - 0078
city: Caba
country: Argentina
facility: Local Institution - 0015
city: Cordoba
country: Argentina
facility: Local Institution - 0119
city: St Leonards
country: Australia
facility: Local Institution - 0118
state: New South Wales
city: Sydney
country: Australia
facility: Local Institution - 0062
state: New South Wales
city: Woolloongabba
country: Australia
facility: Local Institution - 0117
state: Queensland
city: Brussels
country: Belgium
facility: Local Institution - 0112
city: Bruxelles
country: Belgium
facility: Local Institution - 0113
city: Leuven
country: Belgium
facility: Local Institution - 0114
city: Edmonton
country: Canada
facility: Local Institution - 0010
state: Alberta
city: Hamilton
country: Canada
facility: Local Institution - 0060
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0036
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 0088
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0018
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0082
state: Metropolitana
city: Copenhagen
country: Denmark
facility: Local Institution - 0080
city: Herlev
country: Denmark
facility: Local Institution - 0081
city: Lyon Cedex 08
country: France
facility: Local Institution - 0072
city: Marseille Cedex 9
country: France
facility: Local Institution - 0075
city: Paris Cedex 5
country: France
facility: Local Institution - 0073
city: Toulouse
country: France
facility: Local Institution - 0074
city: Villejuif
country: France
facility: Local Institution - 0085
city: Berlin
country: Germany
facility: Local Institution - 0039
city: Bonn
country: Germany
facility: Local Institution - 0001
city: Dresden
country: Germany
facility: Local Institution - 0002
city: Essen
country: Germany
facility: Local Institution - 0086
city: Wuerzburg
country: Germany
facility: Local Institution - 0043
city: Genova
country: Italy
facility: Local Institution - 0032
city: Milano
country: Italy
facility: IRCCS Istituto Nazionale Tumori Milano
city: Napoli
country: Italy
facility: Local Institution - 0029
city: Siena
country: Italy
facility: Local Institution - 0031
city: Rotterdam
country: Netherlands
facility: Local Institution - 0116
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Local Institution - 0115
city: Warszawa
country: Poland
facility: Local Institution - 0076
state: Mazowieckie
city: Gdansk
country: Poland
facility: Local Institution - 0077
city: San Juan
country: Puerto Rico
facility: Fundacion De Investigacion
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0068
state: Cluj
city: Bucuresti
country: Romania
facility: Local Institution - 0069
city: Craiova
country: Romania
facility: Local Institution - 0067
city: Floresti
country: Romania
facility: Local Institution - 0070
city: Timisoara, Timis
country: Romania
facility: Local Institution - 0071
city: Singapore
country: Singapore
facility: Local Institution - 0065
state: Central Singapore
city: Singapore
country: Singapore
facility: Local Institution - 0066
city: Barcelona
country: Spain
facility: Local Institution - 0084
city: Madrid
country: Spain
facility: Local Institution - 0083
city: Pamplona
country: Spain
facility: Local Institution - 0110
city: London
country: United Kingdom
facility: Local Institution - 0106
state: Greater London
city: Preston
country: United Kingdom
facility: Local Institution - 0107
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: