E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Solid tumors |
Tumori solidi |
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E.1.1.1 | Medical condition in easily understood language |
Solid tumors |
Tumori solidi |
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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 | 10065252 |
E.1.2 | Term | Solid tumor |
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 |
The primary objective is to assess the safety and tolerability of BMS- 986179 administered alone and in combination with nivolumab. |
Valutare la sicurezza e la tollerabilità di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab |
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E.2.2 | Secondary objectives of the trial |
-) To characterize the PD activity of BMS-986179 administered alone and in combination with nivolumab -) To assess the preliminary anti-tumor activity of BMS-986179 in combination with nivolumab as measured by ORR, DOR, and progression-free survival rate (PFSR) -) To characterize the PK and immunogenicity of BMS-986179 administered alone and in combination with nivolumab -) To characterize the immunogenicity of nivolumab when administered in combination with BMS-986179 |
• Caratterizzare la farmacodinamica (Pharmacodynamic, PD) di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab • Valutare l’attività antitumorale preliminare di BMS-986179 in monoterapia e in combinazione con nivolumab misurata in base al tasso di risposta obiettiva (Objective Response Rate, ORR), durata della risposta (Duration of Response, DOR) e tasso di sopravvivenza libera da progressione (Progression-Free Survival Rate, PFSR) • Caratterizzare la farmacocinetica (Pharmacokinetics, PK) e l’immunogenicità di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab • Caratterizzare l’immunogenicità di nivolumab somministrato in combinazione con BMS-986179
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Version: 6.0 Date: 20/10/2017 Title: A Phase 1/2a Study of BMS-986179 Administered alone and in Combination with Nivolumab (BMS- 936558) in Subjects with Advanced Solid Tumors. Objectives: Additional research samples and the data they generate are used by BMS researchers, and a variety of collaboration partners, to continue to explore the science behind both our drugs and the causes and mechanism of disease and how to effectively treat patients beyond the timeframe of the study, including their use in the development and/or validation of companion diagnostics to support the use of a particular therapy. These samples and their related data may also be used together with samples and data from other clinical studies to support this expanded research.
Pharmacogenomics Version: 6.0 Date: 20/10/2017 Title: A Phase 1/2a Study of BMS-986179 Administered alone and in Combination with Nivolumab (BMS- 936558) in Subjects with Advanced Solid Tumors. Objectives: Additional research samples and the data they generate are used by BMS researchers, and a variety of collaboration partners, to continue to explore the science behind both our drugs and the causes and mechanism of disease and how to effectively treat patients beyond the timeframe of the study, including their use in the development and/or validation of companion diagnostics to support the use of a particular therapy. These samples and their related data may also be used together with samples and data from other clinical studies to support this expanded research.
Other types of substudies Specify title, date and version of each substudy with relative objectives: Part 1B is a substudy
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Farmacogenetica Versione: 6.0 Data: 20/10/2017 Titolo: Studio di fase 1/2a di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab (BMS-936558) in soggetti con tumori solidi in stadio avanzato, sezione 5.10 del protocollo
Obiettivi: Questi campioni e i dati che saranno generati da questa ricerca addizionale saranno utilizzati dai ricercatori di BMS per continuare ad esplorare le caratteristiche dei farmaci B-MS -986179 e Anti-CD73, le cause e il meccanismo delle patologie in studio e come trattare efficacemente i pazienti oltre la durata dello studio, compreso il loro uso nello sviluppo e/o nella convalida di sistemi diagnostici per supportare l'uso di una particolare terapia. Questi campioni e i relativi dati potrebbero anche essere utilizzato insieme ai campioni e ai dati provenienti da altri studi clinici per ampliare questa ricerca.
Farmacogenomica Versione: 6.0 Data: 20/10/2017 Titolo: Studio di fase 1/2a di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab (BMS-936558) in soggetti con tumori solidi in stadio avanzato, sezione 5.10 del protocollo Obiettivi: Questi campioni e i dati che saranno generati da questa ricerca addizionale saranno utilizzati dai ricercatori di BMS per continuare ad esplorare le caratteristiche dei farmaci B-MS -986179 e Anti-CD73, le cause e il meccanismo delle patologie in studio e come trattare efficacemente i pazienti oltre la durata dello studio, compreso il loro uso nello sviluppo e/o nella convalida di sistemi diagnostici per supportare l'uso di una particolare terapia. Questi campioni e i relativi dati potrebbero anche essere utilizzato insieme ai campioni e ai dati provenienti da altri studi clinici per ampliare questa ricerca.
Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: parte 1B è un sottostudio NOTA: ma non è applicabile in Italia
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E.3 | Principal inclusion criteria |
- Men and women at least 18 years of age - Advanced solid tumors - Eastern Cooperative Oncology Group (ECOG) 0-1 - Acceptable lab testing results - Allow biopsies |
- Uomini e donne di almeno 18 anni di età; - Tumori solidi avanzati; - Eastern Cooperative Oncology Group (ECOG) 0-1 - Risultati dei test di laboratorio accettabili - Consenso all’esecuzione di biopsie
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E.4 | Principal exclusion criteria |
- Central nervous system (CNS) tumors - Uncontrolled or significant cardiovascular diseases - Active or known autoimmune disease - Organ transplant |
- Tumori del sistema nervoso centrale (SNC) - Malattie cardiovascolari non sotto controllo o significative - Malattia autoimmune nota o attiva - Trapianto d'organo
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to assess the safety and tolerability of BMS-986179 administered alone and in combination with nivolumab. The assessment of safety will be based on the incidence of AEs, SAEs, AEs leading to discontinuation, and deaths in relation to initial treatment. In addition, clinical laboratory test abnormalities will be examined. |
L’obiettivo primario è valutare la sicurezza e la tollerabilità di BMS-986179 somministrato in monoterapia e in combinazione con nivolumab. La valutazione della sicurezza sarà basata sull'incidenza di AE, SAE che determineranno la sospensione del trattamento e ai decessi in relazione al trattamento iniziale. Inoltre, saranno valutate le anomalie cliniche nei test di laboratorio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
see above section |
Vedi la sezione di cui sopra |
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E.5.2 | Secondary end point(s) |
The first secondary objective (PD effect of CD73 inhibition) will be measured by CD73 enzyme assays and CD73 IHC in pre- and ontreatment tumor biopsies. The anti-tumor activity of BMS-986179 in combination with nivolumab will be measured by ORR, DOR, and PFSR at 24 weeks and will be based on RECIST 1.1 for solid tumors. These anti-tumor assessments may also be performed periodically on an exploratory basis after the 24-week time point as warranted by the data. Disease assessment with CT and/or MRI as appropriate will be performed at baseline, every 8 weeks from the start of combination treatment for the Q1W, Q2W and Q4W regimens, or every 9 weeks from the start of combination treatment for the Q3W regimen until treatment discontinuation or completion, and then every 12 weeks for the first year until further disease progression, start of a new treatment, lost to follow-up, or death, whichever comes first. The PK will be characterized by assessment of PK parameters of BMS- 986179, and immunogenicity will be assessed by the frequency of positive ADA to BMS-986179 and nivolumab. |
Il primo obiettivo secondario (effetto PD dell'inibizione di CD73) sarà misurato mediante l’analisi enzimatica CD73 e CD73 IHC sui campioni bioptici prima del trattamento e durante il trattamento dello studio.
L'attività antitumorale di BMS-986179 in combinazione con nivolumab sarà misurata da ORR, DOR e PFSR a 24 settimane e sarà basata sul RECIST 1.1 per i tumori solidi. Queste valutazioni antitumorali potranno essere eseguite anche periodicamente su base esplorativa dopo le 24 settimane.
La valutazione della malattia con TC e/o risonanza magnetica sarà eseguita al basale, ogni 8 settimane dall’inizio del trattamento di combinazione per i regimi Q1W, Q2W e Q4W o ogni 9 settimane dall'inizio del trattamento combinato per il regime Q3W fino alla sospensione o al completamento del trattamento, e poi per tutti i regimi ogni 12 settimane per il primo anno fino all'ulteriore progressione della malattia, inizio di un nuovo trattamento, perso al follow-up o alla morte, a seconda dell'evento che si verifica per primo.
La PK sarà caratterizzata dalla valutazione dei parametri PK di BMS- 986179 e l'immunogenicità sarà valutata dalla frequenza di ADA positivo a BMS-986179 e nivolumab.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
see above section. |
Vedi la sezione di cui sopra |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
E.8.1.1 - Randomizzato E.8.1.2 - In aperto |
Randomised:, open |
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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 | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Australia |
Canada |
Israel |
United States |
France |
Germany |
Italy |
Netherlands |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 11 |