Phase 3 Study of Nivolumab or Nivolumab plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma

• Register: EUCTR
• Last refreshed on: 26 July 2021
• Main ID: EUCTR2012-005371-13-IE
• Date of registration: 16/05/2013
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb International Corporation
• Public title: Phase 3 Study of Nivolumab or Nivolumab plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma
• Scientific title: A Phase 3, Randomized, Double- Blind Study of Nivolumab Monotherapy or Nivolumab Combined with Ipilimumab Versus Ipilimumab Monotherapy in Subjects with Previously Untreated, Unresectable or Metastatic Melanoma Pharmacogenetics Blood Sample Protocol Amendment 01, version 1.0, dated 19-Mar-2013
• Date of first enrolment: 23/07/2013
• Target sample size: 1144
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005371-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Czechia, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Romania, Russian Federation, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: GSM-CT
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GSM-CT
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
• Histologically confirmed stage III (unresectable) or stage IV melanoma
• Treatment naïve patients
• Measurable disease by CT or MRI per RECIST 1.1 criteria.
• Tumor tissue from an unresectable or metastatic site of disease for biomarker analyses.
• ECOG PS 0 or 1

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 795
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 349

Exclusion criteria:
• Active brain metastases or leptomeningeal metastases
• Ocular melanoma
• Subjects with active, known or suspected autoimmune disease
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Unresectable or metastatic melanoma
MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Opdivo (100 mg/10 ml)
Product Name: NIVOLUMAB - 10ml vial-CLINICAL
Product Code: BMS-936558
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: NIVOLUMAB
CAS Number: 946414-94-4
Current Sponsor code: BMS-936558-01
Other descriptive name: BMS936558
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Product Name: Ipilimumab
Product Code: BMS-734016
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IPILIMUMAB
CAS Number: 477202-00-9
Current Sponsor code: BMS-734016 / MDX010
Other descriptive name: BMS734016
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: Opdivo (100 mg/10 ml)
Product Name: NIVOLUMAB - 10ml vial- COMMERCIAL
Product Code: BMS-936558
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: NIVOLUMAB
CAS Number: 946414-94-4
Current Sponsor code: BMS-936558-01
Other descriptive name: BMS936558
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: OS: From the beginning of randomization period up to date of event
(expected to be no more than 5 years)
PFS : Time Frame: Baseline (Day 1), Week 12, every 6 weeks thereafter
up to week 49, and then every 12 weeks until disease progression is
documented (Approximately around 5 years)]

Secondary Objective: • ORR
• Differences in OS, PFS and ORR between experimental arms
• PFS and OS based on PD-L1 expression
• Mean changes from baseline in EORTC-QLQ-C30

Main Objective: The purpose of this study is to show that Nivolumab and/or Nivolumab
in combination with Ipilimumab will extend progression free survival
and overall survival compared to Ipilimumab alone.

Primary end point(s): -Endpoint of Overall Survival (OS) in all randomized subjects
-Progression Free Survival (PFS)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • ORR: Baseline, Week 12 every 6 weeks thereafter up to week 49, and
then every 12 weeks until disease progression is documented (expected
to be no more than 5 years)
• OS, PFS, and ORR at the same time points identified for the primary
and first secondary objectives
• PFS and OS at the same time points identified as the primary objective
and PD-L1 expression at Baseline:
• Baseline, every 4 weeks for 6 months, then every 6 weeks until disease
progression is documented, during follow-up (30 days after last dose,
100-114 days after last dose)

Secondary end point(s): • ORR
• Differences in OS, PFS and ORR between experimental arms
• PFS and OS based on PD-L1 expression
• Mean changes from baseline in EORTC-QLQ-C30

Secondary ID(s)

2012-005371-13-BE

CA209-067

NCT01844505

Source(s) of Monetary Support

Bristol-Myers Squibb International Corporation

Ethics review

Status: Approved
Approval date: 23/07/2013
Contact: