E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer |
Carcinoma Polmonare Non a Piccole Cellule |
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E.1.1.1 | Medical condition in easily understood language |
Lung Cancer |
Carcinoma Polmonare |
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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 | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048683 |
E.1.2 | Term | Advanced cancer |
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 characterize the safety of nivolumab administered as a flat dose in combination with weight-based ipilimumab dosing in Cohorts A , B and C. |
Caratterizzare la sicurezza di nivolumab somministrato a dose costante in associazione a ipilimumab somministrato in base al peso corporeo nelle Coorti A, B e C. |
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E.2.2 | Secondary objectives of the trial |
To assess progression-free survival (PFS), overall survival (OS), duration of response (DOR) of nivolumab administered as a flat dose in combination with weight-based ipilimumab dosing in Cohorts A, B, and C. To assess the ORR in Cohorts A, B and C. To assess patient reported outcomes (PROs) in all treated participants. |
Valutare la sopravvivenza libera da progressione (PFS), la sopravvivenza globale (OS) la durata della risposta (DOR) di nivolumab somministrato a dose costante in associazione a ipilimumab somministrato in base al peso corporeo nelle Coorti A, B e C. Valutare ORR nelle Coorti A, B e C. Valutare gli esiti riferiti dal soggetto partecipante (Participant Reported Outcomes (PROs) in tutti i partecipanti trattati. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed Written Informed Consent - Histologically confirmed Stage 4 or recurrent non-small cell lung cancer - Eastern Cooperative Oncology Group (ECOG) score 0-1 (Physically able to carry out light housework or office work through to being fully active as you were before cancer) for cohort A, B and C - No prior systemic anticancer therapy (including EGFR and ALK inhibitors) for cohort A, A1 and C - Tissue or Programmed death-ligand 1 (PD-L1) results available Cohort 1A Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) score 2 or - Eastern Cooperative Oncology Group (ECOG) score 0-1 and one disease specific criteria as listed in the protocol Cohort C Inclusion Criteria: - High Tumor Mutation Burden
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- Consenso Informato scritto - Partecipanti che presentano carcinoma polmonare non a piccole cellule (Non-Small Cell Lung Cancer, NSCLC) documentato istologicamente in Stadio IV o recidivante - Punteggio Eastern Cooperative Oncology Group (ECOG) 0 – 1 (fisicamente in grado di svolgere lavori domestici leggeri o lavoro d'ufficio fino ad essere completamente attivi come prima del cancro) per Coorte A, B e C - Nessuna precedente terapia antitumorale sistemica (inclusi inibitori di EGFR e ALK) per la Coorte A, A1 e C - Risultati disponibili di tessuto o PD-L1 - Criteri di inclusione per la Coorte 1A: punteggio Eastern Cooperative Oncology Group (ECOG) 2 o punteggio del gruppo Eastern Cooperative Oncology Group (ECOG) 0-1 e un criterio specifico di malattia come elencato nel protocollo - Criteri di inclusione per la Coorte C: alto peso di mutazioni tumorali
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E.4 | Principal exclusion criteria |
- Untreated brain metastases - An active malignancy that requires concurrent intervention - Active, known or suspected autoimmune disease - Carcinomatous meningitis, which means there is inflammation of the covering of the brain, caused by cancer |
• metastasi cerebrali non trattate. • neoplasia attiva che richieda un intervento concomitante • malattia autoimmune attiva, nota o sospetta • meningite carcinomatosa, il che significa che c’è un’infiammazione della copertura del cervello causata dal cancro
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of participants who experience high grade AEs (Adverse Events) - Cohorts A, B and C. The select AEs of interest are the following: pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, endocrinopathies, and hypersensitivity/infusion reaction events. Percentage of participants who experience high grade AEs - Cohorts A, B and C |
Numero di partecipanti che presentano un alto grado di eventi avversi (AEs) . -Coorti A, B e C . Gli eventi avversi di interesse selezionati sono i seguenti: polmonite, nefrite interstiziale, diarrea/colite, epatite, eruzione cutanea, endocrinopatie ed eventi di ipersensibilità/reazione all’infusione. Percentuale di partecipanti che presentano un alto grado di eventi avversi (AEs) –Coorte A, B e C. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The analysis is scheduled to occur once all patients have initiated study therapy and have been followed for at least 3 months |
E’ previsto che l’analisi venga effettuata una volta che tutti i partecipanti abbiano iniziato il trattamento in studio e siano stati seguiti per almeno 3 mesi |
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E.5.2 | Secondary end point(s) |
Progression-free survival (PFS) - Cohorts A, B and C Objective Response Rate (ORR) - Cohorts A, B and C Overall survival (OS) - Cohorts A, B, and C Duration of Response (DOR) - Cohorts A, B, and C Participant reported outcomes (PROs): assessment of changes in disease-related symptoms and function dimensions of Health Related Quality of Life (HRQoL) using Functional Assessment of Cancer Therapy-Lung (FACT-L) Number of participants who experience high grade AEs - cohort C Percentage of participants who experience high grade AEs - cohort C |
Sopravvivenza libera da progression (PFS)- Coorti A, B e C Tasso di Risposta Obiettiva (ORR) – Coorti A, B e C Sopravvivenza Complessiva (OS) - Coorti A, B e C Durata di risposta (DOR)- Coorti A, B e C Esiti Riferiti dal Soggetto (PRO) : valutazione dei cambiamenti dei sintomi della malattia e degli ambiti relativi alle funzioni della qualità di vita correlata alla salute (Health Related Quality of Life, HRQoL) utilizzando lo strumento di valutazione funzionale della terapia antitumorale per il polmone (Functional Assessment of Cancer Therapy-Lung, FACT-L) Numero di partecipanti che presentano un alto grado di eventi avversi (AEs) – Coorte C Percentuale di soggetti che presentano un alto grado di eventi avversi (AEs) –Coorte C |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The analysis is scheduled to occur once all patients have initiated study therapy and have been followed for at least 3 months. |
E’ previsto che l’analisi venga effettuata una volta che tutti i partecipanti abbiano iniziato il trattamento in studio e siano stati seguiti per almeno 3 mesi |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 | Information not present in EudraCT |
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 |
Brazil |
Canada |
Chile |
Mexico |
Russian Federation |
Turkey |
United States |
Belgium |
France |
Germany |
Greece |
Hungary |
Italy |
Netherlands |
Poland |
Romania |
Spain |
Switzerland |
United Kingdom |
Czechia |
Argentina |
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E.8.7 | Trial has a data monitoring committee | No |
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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Last Patient Last Visit |
Ultima visita di follow-up dell’ultimo soggetto |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 26 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |