E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic melanoma |
|
E.1.1.1 | Medical condition in easily understood language |
Unresectable or metastatic melanoma |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
• 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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
|
|
E.4 | Principal 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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
-Endpoint of Overall Survival (OS) in all randomized subjects
-Progression Free Survival (PFS) |
|
E.5.1.1 | 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)] |
|
E.5.2 | 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 |
|
E.5.2.1 | 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) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
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 |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study will end once survival follow-up has concluded |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |