E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) |
carcinoma polmonare non a piccole cellule localmente avanzato o metastatico (stadio IIIB-IV) |
|
E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer |
carcinoma polmonare non a piccole cellule |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029514 |
E.1.2 | Term | Non-small cell lung cancer NOS |
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 |
- To assess the efficacy of MEDI4736 treatment in terms of objective response rate (ORR) |
Valutare l'efficacia del trattamento con MEDI4736 in termini di tasso di risposta obiettiva (objective response rate, ORR) |
|
E.2.2 | Secondary objectives of the trial |
- To further assess the efficacy of MEDI4736 in terms of: Duration of response (DoR), Progression free survival (PFS), Disease control rate (DCR), Overall survival (OS), and Deep sustained response (DSR)
- To assess the safety, tolerability, PK and immunogenicity profile of MEDI4736 |
- Valutare ulteriormente l'efficacia di MEDI4736 in termini di: durata della risposta (Duration of Response, DoR) , sopravvivenza libera da malattia (Progression Free Survival, PFS), tasso di controllo della malattia (Disease Control Rate, DCR), sopravvivenza globale (Overall Survival, OS) e risposta profonda sostenuta (Deep Sustained Response, DSR)
- Valutare il profilo di sicurezza, tollerabilità, PK e immunogenicità di MEDI4736
|
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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 Research |
Ricerca farmacogenetica |
|
E.3 | Principal inclusion criteria |
1. Provision of signed, written and dated informed consent prior to any study specific procedures
2. Male or female aged 18 years or older
3. Patients must have EITHER
• Histologically- or cytologically-documented NSCLC), OR
• Recurrent or progressive disease following multimodal therapy for locally advanced disease)
4. Patients must have received at least 2 prior systemic treatment regimens for treatment of NSCLC
5. Patients must have experienced disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional systemic therapy
6. Patients must provide a tumour sample
7. Patients must have measurable disease
8. Life expectancy ≥12 weeks
9. World Health Organisation (WHO) Performance Status of 0 or 1
10. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients
11. Adequate organ and marrow function |
1. Fornire un consenso informato scritto, firmato e datato prima di qualsiasi procedura specifica dello studio.
2. Pazienti di sesso maschile o femminile di età pari o superiore ai 18 anni
3. I pazienti devono presentare:
- NSCLC documentato istologicamente o citologicamente, OPPURE
- Malattia recidiva o progressiva in seguito a terapia multimodale per malattia localmente avanzata
4. I pazienti devono aver ricevuto almeno 2 precedenti regimi di trattamento sistemici per il trattamento dell'NSCLC.
5. I pazienti devono aver presentato progressione della malattia o ricorrenza dopo un regime chemioterapico a base di platino e almeno 1 terapia sistemica aggiuntiva
6. I pazienti devono fornire un campione del tumore
7. I pazienti devono presentare malattia misurabile
8. Aspettativa di vita ≥12 settimane
9. Performance Status di 0 o 1 secondo l'Organizzazione mondiale della sanità (OMS)
10. Evidenza di stato post-menopausale o test di gravidanza sul siero o sulle urine negativo per le pazienti pre-menopausali
11. Funzione d'organo e midollare adeguata
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E.4 | Principal exclusion criteria |
1. Participation in another clinical study with an investigational product (IMP) during the last 4 weeks
2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
3. Mixed small cell and NSCLC histology
4. Receipt of any immunotherapy, or IMP within 4 weeks prior to the first dose of study drug
5. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
6. Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy
7. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
8. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
9. Receipt of radiation therapy within 4 weeks prior to starting MEDI4736, or limited field of radiation for palliation within 2 weeks of the first dose of MEDI4736
10. Recent major surgery within 4 weeks
11. Active or prior documented autoimmune disease within the past 2 years, except for: Vitiligo, Grave's disease, or psoriasis not requiring systemic treatment
12. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
13. History of primary immunodeficiency
14. History of organ transplant that requires therapeutic
Immunosuppression
15. History of hypersensitivity to MEDI4736 or any excipient
16. Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study
17. Uncontrolled intercurrent illness
18. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736
19. History of another primary malignancy within 5 years prior to starting MEDI4736, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
20. Female patients who are pregnant or breast-feeding. Male or female patients of reproductive potential who are not using an effective method of birth control
21. Any condition that, in the opinion of the investigator, would interfere with evaluation of MEDI4736 or interpretation of patient safety or study results |
1. Partecipazione a un altro studio clinico con un prodotto sperimentale durante le ultime 4 settimane
2. Arruolamento concomitante in un altro studio clinico, salvo qualora si tratti di uno studio clinico osservazionale (non interventistico) o del periodo di follow-up di uno studio interventistico
3. Istologia mista a piccole cellule e NSCLC
4. Aver ricevuto qualsiasi immunoterapia o farmaco sperimentale nelle 4 settimane precedenti la prima dose di farmaco dello studio
5. Esposizione precedente a qualsiasi anticorpo anti-PD-1 o anti-PD-L1
6. Qualsiasi tossicità non risolta di grado >2 CTCAE derivante da una precedente terapia antitumorale.
7. Qualsiasi evento avverso immuno-correlato (immune-related adverse event, irAE) precedente di grado ≥3 verificatosi durante il trattamento con qualsiasi agente immunoterapico precedente o qualsiasi irAE di grado >1 non risolto.
8. Qualsiasi chemioterapia, immunoterapia, terapia biologica od ormonale concomitante per il trattamento del carcinoma.
9. Aver ricevuto radioterapia nelle 4 settimane precedenti l'inizio dell’assunzione del prodotto sperimentale o di radiazioni a campo ristretto a fini palliativi entro 2 settimane dalla prima dose di farmaco sperimentale
10. Recente intervento chirurgico maggiore nelle 4 settimane precedenti
11. Malattia autoimmune attiva o pregressa documentata nei 2 anni precedenti, tranne i pazienti con vitiligine, malattia di Grave o psoriasi che non richiede trattamento sistemico
12. Malattia intestinale infiammatoria attiva o pregressa documentata (es. morbo di Crohn, colite ulcerosa)
13. Anamnesi di immunodeficienza primaria
14. Anamnesi di trapianto di organo che richiede immunosoppressione terapeutica
15. Anamnesi di ipersensibilità a MEDI4736 o a uno qualsiasi degli eccipienti
16. Metastasi al cervello o compressione del midollo spinale salvo ove asintomatiche, trattate e stabilmente senza trattamento con steroidi e anticonvulsivanti da almeno 1 mese prima dell'ingresso nello studio
17. Malattia intercorrente non controllata
18. Aver ricevuto vaccino vivo attenuato nei 30 giorni precedenti l'ingresso nello studio o entro 30 giorni dalla ricezione di MEDI4736
19. Anamnesi di altra neoplasia maligna primaria nei 5 anni precedenti l'inizio del prodotto sperimentale, eccetto carcinoma a cellule basali o squamose della pelle trattato adeguatamente o carcinoma della cervice in situ e malattia in studio.
20. Pazienti di sesso femminile in gravidanza, allattamento o pazienti di sesso maschile o femminile potenzialmente fertili che non utilizzano un metodo efficace di controllo delle nascite.
21. Qualsiasi condizione che, nel parere dello Sperimentatore, interferirebbe con la valutazione del prodotto sperimentale o l'interpretazione dei risultati della sicurezza per il paziente o con i risultati dello studio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) (per RECIST 1.1) |
tasso di risposta obiettiva (objective response rate, ORR) (secondo i criteri RECIST 1.1) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The data cut-off for analysis of ORR will take place approximately 8 months after recruitment ends. |
il cut-off dei dati per l'analisi dell'ORR avverrà circa 8 mesi dopo il termine del reclutamento. |
|
E.5.2 | Secondary end point(s) |
- Duration of response
- Progression free survival
- Disease control rate
- Overall survival
- Deep sustained response
- AEs |
- durata della risposta
- sopravvivenza libera da malattia
- tasso di controllo della malattia
- sopravvivenza globale
- risposta profonda sostenuta
- eventi avversi
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The data cut-off for analysis of the secondary efficacy endpoints will take place approximately 8 months after recruitment ends. The final analysis of OS (secondary endpoint) will take place 12 months after recruitment ends. |
il cut-off dei dati per l'analisi degli endpoints secondari di efficacia avverrà circa 8 mesi dopo il termine del reclutamento. L'analisi finale della OS (endpoint secondario) avrà luogo 12 mesi dopo il termine dell'arruolamento. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 57 |
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 |
Canada |
European Union |
Japan |
Korea, Republic of |
Malaysia |
Philippines |
United States |
|
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
|
The end of the study is defined as ‘the last visit of the last patient undergoing the study’. |
La fine dello studio è definita come “l’ultima vista dell’ultimo soggetto in studio”. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |