E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) |
Pazienti con carcinoma polmonare non a piccole cellule (NSCLC) non resecabile e localmente avanzato (stadio III) |
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E.1.1.1 | Medical condition in easily understood language |
Specific type of lung cancer called "Non-Small Cell Lung Cancer" (NSCLC) that cannot be removed by surgery |
Tipo specifico di cancro del polmone chiamato "carcinoma polmonare non a piccole cellule" (NSCLC) che non può essere rimosso chirurgicamente |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To demonstrate superiority of durvalumab + oleclumab relative to durvalumab + placebo in participants with unresectable, Stage III NSCLC who have not progressed on prior platinum-based cCRT • Assessment by PFS as assessed by BICR
2. To demonstrate superiority of durvalumab + monalizumab relative to durvalumab + placebo in participants with unresectable, Stage III NSCLC who have not progressed on prior platinum-based cCRT • Assessment by PFS as assessed by BICR |
1. Dimostrare la superiorità di durvalumab + oleclumab rispetto a durvalumab + placebo nei partecipanti con NSCLC non resecabile di stadio III che non sono progrediti dopo una precedente cCRT a base di platino • Valutazione della PFS valutata dal BICR
2. Dimostrare la superiorità di durvalumab + monalizumab rispetto a durvalumab + placebo nei partecipanti con NSCLC non resecabile di stadio III che non sono progrediti dopo una precedente cCRT a base di platino • Valutazione della PFS valutata dal BICR |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate superiority of durvalumab+oleclumab & durvalumab+monalizumab relative to durvalumab+placebo in patients with unresectable Stage III NSCLC who have not progressed on prior platinum-based cCRT; assessment by OS, OS24, ORR, DoR, PFS6, PFS12, PFS18, PFS24, PFS2, TTDM, TFST, PFS as assessed by Investigator To investigate relationship between patient's PD-L1 expression on tumor cells & efficacy outcomes with durvalumab+oleclumab, durvalumab+monalizumab & durvalumab+placebo - To assess PK of durvalumab when in combination with oleclumab & with monalizumab - To assess PK of oleclumab when in combination with durvalumab - To assess PK of monalizumab when in combination with durvalumab - To investigate immunogenicity of durvalumab,oleclumab & monalizumab - To assess time to deterioration in pulmonary symptoms |
- Dimostrare la superiorità di durvalumab + oleclumab e durvalumab + monalizumab rispetto a durvalumab + placebo nei pazienti con NSCLC non resecabile di stadio III che non sono progrediti dopo cCRT a base di platino; valutazione dell’ OS, OS24, ORR, DoR, PFS6, PFS12, PFS18, PFS24, PFS2, TTDM, TFST, PFS come valutati dallo sperimentatore. - Studiare la relazione tra l'espressione di PD-L1 sulle cellule tumorali del paziente ed i risultati di efficacia con durvalumab+oleclumab, durvalumab+monalizumab e durvalumab+placebo - Valutare la farmacocinetica di durvalumab in combinazione con oleclumab e con monalizumab - Valutare la farmacocinetica di oleclumab in combinazione con durvalumab - Valutare la farmacocinetica di monalizumab in combinazione con durvalumab - Studiare l'immunogenicità di durvalumab, oleclumab e monalizumab - Valutare il tempo al deterioramento dei sintomi polmonari |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must be = 18 years at the time of screening. - Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease - Provision of a tumour tissue sample obtained prior to CRT - Documented tumour PD-L1 status by central lab - Documented EGFR and ALK wild-type status (local or central). - Patients must not have progressed following definitive, platinumbased, concurrent chemoradiotherapy - Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy - Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique. - WHO performance status of 0 or 1 at randomization - Adequate organ and marrow function |
- Il partecipante deve avere = 18 anni al momento dello screening. - NSCLC istologicamente o citologicamente documentato e trattate con CRT concomitante per malattia localmente avanzata, non resecabile (di stadio III) - Fornitura di un campione di tessuto tumorale ottenuto prima della CRT - Stato del tumore per PD-L1 documentato dal laboratorio centrale - Stato documentato di EGFR e ALK wild-type (locale o centrale). - I pazienti non devono essere progrediti dopo la chemioradioterapia concomitante definitiva, a base di platino. - I partecipanti devono aver ricevuto almeno 2 cicli di chemioterapia a base di platino in concomitanza con radioterapia - I partecipanti devono aver ricevuto una dose totale di radiazioni di 60 Gy ±10% (da 54 Gy a 66 Gy) come parte della chemioradioterapia, per essere randomizzati. La radioterapia dovrebbe essere somministrata ad intensità modulata (preferita) o con tecnica conforme 3D. - Performance status dell'OMS di 0 o 1 alla randomizzazione - Adeguata funzionalità degli organi e del midollo |
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E.4 | Principal exclusion criteria |
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease > 5 years before the first dose of study intervention and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, adequately treated carcinoma in situ or Ta tumours treated with curative intent and without evidence of disease. - Mixed small cell and non-small cell lung cancer histology. - Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC. - Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT. - Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia). - Participants with =grade 2 pneumonitis from prior chemoradiation therapy. - History of idiopathic pulmonary fibrosis, organizing pneumonia, druginduced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural effusion, or pulmonary fibrosis diagnosed in the past 6 months prior to randomization. - Active or prior documented autoimmune or inflammatory disorders (with exceptions) - Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. |
- Storia di un altro tumore maligno primario ad eccezione del tumore maligno trattato con intento curativo senza malattia attiva nota > 5 anni prima della prima dose del farmaco in studio e di basso rischio potenziale di recidiva, carcinoma a cellule basali della pelle, carcinoma a cellule squamose della pelle o lentigo maligna sottoposta a terapia potenzialmente curativa, carcinoma in situ adeguatamente trattato o tumori Ta trattati con curativo intento e senza evidenza di malattia. - Istologia mista del carcinoma polmonare a piccole cellule e non a piccole cellule. - Partecipanti che ricevono in sequenza (non comprensiva di induzione) chemioradioterapia per NSCLC localmente avanzati (Stadio III) non resecabili. - Partecipanti con NSCLC localmente avanzato (Stadio III) non resecabile che sono progrediti durante cCRT a base di platino. - Qualsiasi tossicità irrisolta CTCAE >Grado 2 dalla precedente chemioradioterapia (esclusa l'alopecia). - Partecipanti con polmonite di grado = 2 da precedente chemioradioterapia. - Storia di fibrosi polmonare idiopatica, polmonite organizzata, polmonite farmacoindotta, o polmonite idiopatica, o evidenza di polmonite attiva, ILD, versamento pleurico o fibrosi polmonare diagnosticata negli ultimi 6 mesi prima della randomizzazione. - Disturbi autoimmuni o infiammatori attivi o precedentemente documentati (con eccezioni) - Uso attuale o precedente di farmaci immunosoppressori entro 14 giorni prima della prima dose di durvalumab. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1. |
Sopravvivenza libera da progressione (PFS) valutata da BICR, secondo RECIST 1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 5 years after first patient randomized |
fino a 5 anni dopo la randomizzazione del primo paziente |
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E.5.2 | Secondary end point(s) |
1. Overall survival (OS) 2. Overall survival (OS) at 24 months 3. Objective response rate (ORR) per RECIST 1.1 as assessed by BICR 4. Duration of response (DoR) per RECIST 1.1 as assessed by BICR 5. Progression free survival (PFS) at 6, 12, 18, and 24 months respectively, per RECIST 1.1 as assessed by BICR 6. Time from randomization to second progression (PFS2) 7. Time from randomization to first date of distant metastasis or death (TTDM) 8. Time from randomization to start date of first subsequent therapy (TFST) 9. Progression free survival (PFS) as assessed by Investigator 10. IHC analysis of PD-L1 TC expression relative to efficacy outcomes 11. The pharmacokinetics (PK) of durvalumab, oleclumab, and monalizumab as determined by concentration 12. The immunogenicity of durvalumab, oleclumab, and monalizumab as assessed by presence of anti-drug antibodies (ADAs) 13. Time to deterioration in pulmonary symptoms (TTFCD) |
1. Sopravvivenza globale (OS) 2. Sopravvivenza globale (OS) a 24 mesi 3. Tasso di risposta obiettiva (ORR) secondo RECIST 1.1 come valutato da BICR 4. Durata della risposta (DoR) secondo RECIST 1.1 valutata da BICR 5. Sopravvivenza libera da progressione (PFS) a 6, 12, 18 e 24 mesi rispettivamente, secondo RECIST1.1 come valutato da BICR 6. Tempo dalla randomizzazione alla seconda progressione (PFS2) 7. Tempo dalla randomizzazione alla prima data di metastasi a distanza o morte (TTDM) 8. Tempo dalla randomizzazione alla data di inizio della prima terapia successiva (TFST) 9. Sopravvivenza libera da progressione (PFS) valutata dallo sperimentatore 10. Analisi IHC dell'espressione di PD-L1 TC relativa ai risultati di efficacia 11. La farmacocinetica (PK) di durvalumab, oleclumab e monalizumab determinata dalla concentrazione 12. L'immunogenicità di durvalumab, oleclumab e monalizumab come valutata dalla presenza di anticorpi anti-farmaco (ADA) 13. Tempo al deterioramento dei sintomi polmonari (TTFCD) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ORR, DoR, PFS6, PFS12, PFS18, PFS24, PFS2, TTDM, TFST, PFS: Up to 5 years after first patient randomized OS, OS24: Up to 9 years after first patient randomized ADA, PK: From date of randomization until 3 months after date of last IP dose NSCLC-SAQ: Up to 5 years after last patient randomized |
ORR, DoR, PFS6, PFS12, PFS18, PFS24, PFS2, TTDM, TFST, PFS: fino a 5 anni dopo la randomizzazione del primo paziente OS, OS24: Fino a 9 anni dopo la randomizzazione del primo paziente ADA, PK: dalla data di randomizzazione fino a 3 mesi dopo la data dell'ultima somministrazione del farmaco di studio NSCLC-SAQ: fino a 5 anni dopo la randomizzazione dell’ultimo paziente |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Symptoms and health-related Quality of Life, Tolerability |
Sintomi e qualità della vita correlata alla salute, Tollerabilità |
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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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 46 |
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 |
Brazil |
Canada |
China |
Colombia |
Japan |
Korea, Republic of |
Peru |
Russian Federation |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
Viet Nam |
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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 end of the study is defined as the date of the last expected visit/contact of the last participant in the study globally. A participant is considered to have completed the study if he/she has completed all phases of the study including the last expected visit. |
La fine dello studio è definita come la data dell'ultima visita attesa /contatto dell'ultimo partecipante allo studio a livello globale. Si considera che un partecipante abbia completato lo studio se ha completato tutte le fasi dello studio inclusa l'ultima visita prevista. |
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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 | 9 |
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 | 9 |
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 |