E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung cancer (NSCLC) |
Carcinoma polmonare non a piccole cellule (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
NSCLC is the most common type of lung cancer that originally arises from the lungs and could spread to areas near the lungs or distantly to other organs. |
L'NSCLC è il tipo più comune di tumore polmonare insorto originariamente dai polmoni e che potrebbe diffondersi in aree vicine ai polmoni o ad altri organi distanti da questi ultimi. |
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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 | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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 | 21.1 |
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 |
To evaluate the efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab on the basis of the progression-free survival (PFS) and overall survival (OS) nella popolazione di analisi primaria. |
Valutare l’efficacia e la sicurezza di tiragolumab + atezolizumab rispetto a placebo + atezolizumab sulla base della sopravvivenza libera da progressione progressione (PFS) e della sopravvivenza globale (OS) in the primary analysis population. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab on the basis of the Investigator assessed PFS and OS in the secondary analysis population and in patients with high tumor PD-L1 expression, confirmed overall response rate (ORR), duration of response (DOR), PFS rate at 6 months and 12 months, OS rate at 12 months and 24 months, time to confirmed deterioration and global health status/quality of life • To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with placebo plus atezolizumab • To characterize pharmacokinetics of tiragolumab and atezolizumab • To evaluate the immune response to tiragolumab plus atezolizumab. |
• Valutare l'efficacia di tiragolumab più atezolizumab rispetto a placebo più atezolizumab sulla base della valutazione del medico di studio su PFS e OS nella popolazione di analisi secondaria e nei pazienti con un'alta espressione di PD-L1, ORR confermata, DOR confermata, tasso di PFS a 6 mesi e 12 mesi, tasso di SO a 12 e 24 mesi, tempo di peggioramento confermato e stato di salute globale/QoL • Valutare la sicurezza e la tollerabilità di tiragolumab più atezolizumab rispetto al placebo più atezolizumab • Caratterizzare la farmacocinetica di tiragolumab e atezolizumab • Valutare la risposta immunitaria al tiragolumab più atezolizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Histologically or cytologically documented locally advanced or recurrent NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy, or metastatic Stage IV NSCLC - No prior systemic treatment for metastatic NSCLC - Tumor PD-L1 expression as determined by PD-L1 IHC assay TPS >= 50% as determined by 22C3 pharmaDx assay TC3 or IC3 as determined by the VENTANA PD-L1 Assay (SP142), or TC >= 50% as determined by the investigational VENTANA PD-L1 CDx Assay (SP263) of tumor tissue - Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) - Adequate hematologic and end-organ function. |
- Età> = 18 anni - Stato delle prestazioni del gruppo di oncologia della cooperativa orientale pari a 0 o 1 - NSCLC localmente avanzato o recidivante documentato dall’esame istologico o citologico non idoneo a chirurgia curativa e/o radioterapia definitiva con o senza chemioterapia o NSCLC metastatico in stadio IV - Nessun precedente trattamento sistemico per NSCLC metastatico - Espressione tumorale di PD-L1 determinata mediante il saggio PD-L1 IHC TPS >= 50% come determinato dal saggio 22C3 pharmaDx TC3 o IC3 come determinato dal saggio VENTANA PD-L1 (SP142), o TC >= 50% come determinato dal test VENTANA PD-L1 CDx (SP263) del tessuto tumorale rappresentativo - Malattia misurabile per criteri di valutazione della risposta nei tumori solidi, versione 1.1 (RECIST v1.1) - Adeguata funzione ematologica e degli organi terminali. |
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E.4 | Principal exclusion criteria |
- Known to have a mutation in the EGFR gene or an ALK fusion oncogene - Symptomatic, untreated, or actively progressing central nervous system metastases - Active or history of autoimmune disease or immune deficiency - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis - Significant cardiovascular disease - History of malignancy other than NSCLC within 5 years, with the exception of malignancies with a negligible risk of metastasis or death treated with curative intent - Severe infection within 4 weeks prior to initiation of study treatment - Positive test result for human immunodeficiency virus (HIV) - Active hepatitis B or hepatitis C infection - Treatment with investigational therapy within 28 days prior to initiation of study treatment - Prior treatment with CD137 agonists or immune checkpoint blockade therapies - Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to initiation of study treatment. |
- Paziente conosciuto per avere una mutazione nel gene EGFR o un oncogene di fusione ALK - Metastasi del sistema nervoso centrale sintomatiche, non trattate o in fase di avanzamento attivo - Malattia autoimmune o immunodeficienza attiva o pregressa - Storia di fibrosi polmonare idiopatica, polmonite organizzativa, polmonite indotta da farmaci o polmonite idiopatica oppure evidenza di polmonite attiva - Malattie cardiovascolari significative - Anamnesi positiva per neoplasia maligna diversa dall’NSCLC nei 5 anni precedenti la randomizzazione, ad eccezione dei tumori maligni con un rischio trascurabile di metastasi o morte - Infezione severa entro 4 settimane prima dell'inizio del trattamento in studio - Test positivo per il virus dell’immunodeficienza umana (HIV) - Epatite B attiva o infezione da epatite C. - Trattamento con terapia sperimentale nei 28 giorni precedenti l'inizio del trattamento in studio - Trattamento precedente con agonisti CD137 o terapie con blocco del checkpoint immunitario - Trattamento con immunostimolanti sistemici o precedente trattamento con immunosoppressori sistemici nelle 4 settimane o nelle 5 emivite di eliminazione del farmaco prima dell'inizio del trattamento in studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. PFS as determined by the investigator according to RECIST v1.1 nella popolazione di analisi primaria 2. OS nella popolazione di analisi primaria |
1. PFS come determinato dallo sperimentatore secondo RECIST v1.1 in the primary analysis population 2. OS in the primary analysis population |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to 59 months |
1-2. Fino a 59 mesi |
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E.5.2 | Secondary end point(s) |
1. Investigator assessed PFS according to RECIST v1.1 in the secondary analysis population 2. Investigator assessed OS according to RECIST v1.1 in the secondary analysis population 3. Investigator assessed PFS according to RECIST v1.1 in patients with high tumor PD-L1 expression, as determined by the investigational VENTANA PD L1 (SP263) CDx Assay 4.Investigator assessed OS according to RECIST v1.1 in patients with high tumor PD-L1 expression, as determined by the investigational VENTANA PD L1 (SP263) CDx Assay 5. Confirmed ORR as determined by the investigator according to RECIST v1.1 6. DOR for patients with confirmed ORR as determined by the investigator according to RECIST v1.1 7. PFS rate at 6 months and 12 months as determined by the investigator according to RECIST v1.1 8. OS rate at 12 months and 24 months 9. Time of confirmed deterioration in patient-reported physical functioning and global health status/quality of life, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 10. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 11. Minimum serum concentration (Cmin) and Maximum serum concentrate (Cmax) of tiragolumab 12. Cmin and Cmax of atezolizumab 13. Prevalence of ADAs to tiragolumab and atezolizumab at baseline and during the study. |
1. Lo sperimentatore ha valutato la PFS secondo RECIST v1.1 nella popolazione dell'analisi secondaria 2. OS valutata dallo sperimentatore secondo RECIST v1.1 nella popolazione dell'analisi secondaria 3. Lo sperimentatore ha valutato la PFS secondo RECIST v1.1 in pazienti con elevata espressione tumorale di PD-L1, come determinato dal test CDx VENTANA PD L1 (SP263) sperimentale 4 Lo sperimentatore ha valutato la OS secondo RECIST v1.1 in pazienti con elevata espressione tumorale di PD-L1, come determinato dal test CDx VENTANA PD L1 (SP263) sperimentale 5. ORR confermato come determinato dall'investigatore secondo RECIST v1.1 6. DOR nei pazienti con ORR confermata come determinato dallo sperimentatore secondo RECIST v1.1 7. Tasso di PFS a 6 e 12 mesi determinato dallo sperimentatore secondo RECIST v1.1 8. Tasso di OS a 12 e 24 mesi 9. Tempo al peggioramento confermato nel fisico riportato dal paziente, funzionamento e stato di salute globale/QoL, misurato dal questionario dell’Organizzazione Europea per la Ricerca e il Trattamento della Qualità della vita per il cancro 10. Incidenza e gravità degli eventi avversi, con gravità determinata secondo i criteri terminologici comuni del National Cancer Institute per eventi avversi, versione 5.0 11. Concentrazione sierica minima (Cmin) e massima (Cmax) di tiragolumab 12. Cmin e Cmax di atezolizumab 13. Prevalenza di ADA rispetto a tiragolumab e atezolizumab al basale e durante lo studio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-9. Up to 59 months |
1-9. Fino a 59 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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
immune response |
risposta immunitaria |
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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 | 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 | Yes |
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
| 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
China |
Japan |
Korea, Republic of |
Mexico |
Peru |
Russian Federation |
Serbia |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
Austria |
Denmark |
Germany |
Greece |
Hungary |
Italy |
Netherlands |
Poland |
Spain |
Switzerland |
Argentina |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 59 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 59 |
E.8.9.2 | In all countries concerned by the trial days | 0 |