E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Renal Cell Carcinoma with Intermediate- or Poor-Risk Factors |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067946 |
E.1.2 | Term | Renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
- To compare the PFS using RECIST 1.1 of nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants
- To compare the ORR using RECIST 1.1 of nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants |
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E.2.2 | Secondary objectives of the trial |
- To compare the OS of nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants
- To evaluate additional efficacy measures in all randomized participants.
- To estimate the incidence of AEs of nivolumab combined with ipilimumab and nivolumab and placebo in all treated participants
- To investigate whether gene expression (GEP) signatures related to clear cell RCC (ccRCC) enrich for clinical benefit with nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants
- To explore association of baseline PD-L1 expression on tumor with clinical benefit |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histological confirmation of renal carcinoma with clear cell component including participants who may have sarcomatoid features.
- Advanced (not amenable to curative surgery or radiation therapy) renal cell carcinoma (RCC) or metastatic RCC (mRCC).
- Measurable disease by CT or MRI per RECIST 1.1 criteria.
- No prior systemic therapy for RCC
- Must be intermediate or poor risk as per International Metastatic RCC Database Consortium (IMDC). |
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E.4 | Principal exclusion criteria |
- Any active central nervous system (CNS) metastases.
- Active, known, or suspected autoimmune disease
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA-4 antibody, or any other agents specifically targeting T-cell co stimulation or checkpoint pathways
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression free survival (PFS) by BICR
2. Overall Response Rate (ORR) by BICR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 34 months
2. Up to 23 months |
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E.5.2 | Secondary end point(s) |
3. Overall survival (OS)
4. Overall response rate (ORR) by Investigator
5. Disease control rate (DCR) by Investigator and by blinded independent central review (BICR)
6. Duration of response (DoR) by Investigator and by blinded independent central review (BICR)
7. Time to objective response (TTR) by Investigator and by blinded independent central review (BICR)
8. Progression free survival (PFS) and PFS2 per Investigator
9. Incidence of adverse events (AEs), Serious Adverse Events, drug -related SAEs and significant changes in laboratory tests (Hematology tests, Coagulation tests), Clinical Chemistry Tests and Serology Tests)
10. PFS, ORR and OS based on GEP signatures
11. Overall Survival based on programmed cell death protein ligand-1 (PD-L1) expression
12. Overall response rate (ORR) by BICR based on PD-L1 expression
13. Progression Free Survival (PFS) by BICR based on PD-L1 expression)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3. Up to 5 years
4. Up to 4 years
5. Up to 4 years
6. Up to 4 years
7. Up to 4 years
8. Up to 4 years
9. Up to 4 years
10. Up to 4 years
11. Up to 4 Years
12. Up to 4 Years
13. Up to 4 Years |
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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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
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 |
Argentina |
Chile |
Mexico |
Austria |
France |
Poland |
Romania |
Spain |
Czechia |
Greece |
Italy |
Ireland |
Portugal |
Russian Federation |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 21 |