E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Clear Cell Renal Cell Carcinoma |
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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 | LLT |
E.1.2 | Classification code | 10050076 |
E.1.2 | Term | Metastatic renal carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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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 demonstrate PK noninferiority of SC nivolumab vs IV nivolumab administration |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate the ORR noninferiority of SC nivolumab vs IV nivolumab administration. 2. To evaluate efficacy of SC nivolumab over 12 months. 3. To evaluate PK of SC nivolumab and IV nivolumab administration. 4. To evaluate the safety profile of SC nivolumab and IV nivolumab administration. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: -Histological confirmation of renal cell carcinoma (RCC) with a clear cell component, including participants who may also have sarcomatoid features. -Advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC (Stage IV). -Measurable disease as defined by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 criteria within 28 days prior to randomization. -Received no more than 2 prior systemic treatment regimens. -Intolerance or progression on or after the last treatment regimen received and within 6 months prior to randomization on the study. -Karnofsky PS ≥ 70 at screening. -Must agree to follow specific methods of contraception, if applicable. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria: -Untreated, symptomatic central nervous system (CNS) metastases. -Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to randomization. -Active, known, or suspected autoimmune disease. -Known human immunodeficiency virus (HIV) positive with an acquired immunodeficiency syndrome -(AIDS) defining opportunistic infection within the last year, or a current CD4 count < 350 cells/μL. Participants with HIV are eligible if: 1. They have received established antiretroviral therapy (ART) for at least 4 weeks prior to randomization. 2. They continue on ART as clinically indicated while enrolled on study. 3. CD4 counts and viral load are monitored per standard of care by a local healthcare provider. 4. Inclusion of participants with HIV should be based on Investigator clinical judgment in consultation with the Medical Monitor. NOTE: Testing for HIV must be performed at sites where mandated locally. HIV- positive participants must be excluded where mandated locally. -Serious or uncontrolled medical disorders including for example, active severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) infection within approximately 4 weeks prior to screening. In the case of prior SARS-CoV-2 infection, acute symptoms must have resolved based on investigator clinical judgment and, in consultation with Medical Monitor, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment to be eligible. -Prior treatment with a programmed death receptor-1 (anti-PD-1), programmed death ligand-1 (anti-PD-L1), or cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways. -Treatment with any live attenuated vaccine within 30 days of first study treatment -Other protocol-defined inclusion/exclusion criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time-averaged serum concentration over 28 days (Cavgd28) Trough serum concentration at steady-state (Cminss)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time-averaged serum concentration over 28 days (Cavgd28) [ Time Frame: Up to 28 days ] Trough serum concentration at steady-state (Cminss) [ Time Frame: Up to 4 months ] |
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E.5.2 | Secondary end point(s) |
-Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ] -Trough serum concentration at day 28 (Cmind28) [ Time Frame: At 28 days ] -Maximum serum concentration after the first dose (Cmax1) [ Time Frame: Up to 7 days ] -Peak serum concentration at steady-state (Cmaxss) [ Time Frame: Up to 4 months ] -Steady-state average serum concentration (Cavgss) [ Time Frame: Up to 4 months ] -Observed trough nivolumab serum concentration (Ctrough) at Week 17 [ Time Frame: At Week 17 ] -Incidence of adverse events (AEs) [ Time Frame: Up to 2 years 3 months ] -Incidence of serious adverse events (SAEs) [ Time Frame: Up to 2 years 3 months ] -Incidence of AEs leading to discontinuation [ Time Frame: Up to 2 years ] -Incidence of deaths [ Time Frame: Up to 5 years ] -Incidence of clinically significant changes in clinical laboratory results: Hematology tests [ Time Frame: Up to 2 years 3 months ] -Incidence of clinically significant changes in clinical laboratory results: Chemistry panel tests [ Time Frame: Up to 2 years 3 months ] -Efficacy parameters: disease control rate (DCR) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ] -Efficacy parameters: DCR by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ] -Efficacy parameters: DCR by BICR at end of study [ Time Frame: Up to 5 years ] -Efficacy parameters: duration of response (DOR) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ] -Efficacy parameters: DOR by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ] -Efficacy parameters: DOR by BICR at end of study [ Time Frame: Up to 5 years ] -Efficacy parameters: time to objective response (TTR) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ] -Efficacy parameters: TTR by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ] -Efficacy parameters: TTR by BICR at end of study [ Time Frame: Up to 5 years ] -Efficacy parameters: progression-free survival (PFS) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ] -Efficacy parameters: PFS by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ] -Efficacy parameters: PFS by BICR at end of study [ Time Frame: Up to 5 years ] -Efficacy parameters: overall survival (OS) with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ] -Efficacy parameters: OS with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ] -Efficacy parameters: OS at end of study [ Time Frame: Up to 5 years ] -Efficacy parameters: ORR by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ] -Efficacy parameters: ORR by BICR at end of study [ Time Frame: Up to 5 years ] -Incidence of anaphylactic, hypersensitivity, and systemic infusion reactions [ Time Frame: Up to 2 years 3 months ] -Incidence of local injection- or infusion-site reactions [ Time Frame: Up to 2 years 3 months ] -Percentage of participants who develop anti-nivolumab antibodies, if applicable [ Time Frame: Up to 2 years 3 months ] -Percentage of participants who develop neutralizing antibodies, if applicable [ Time Frame: Up to 2 years 3 months ] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints for Secondary end points are mentioned in the above section
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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 | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
New Zealand |
Ireland |
Brazil |
Czechia |
Finland |
France |
Italy |
Mexico |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Turkey |
United States |
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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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The time when the clinical cutoff for the final overall survival (OS) analysis has been achieved, which is 3 years after the date of the last participant's first dose |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |