E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous cell carcinoma of the head and neck (SCCHN). |
Carcinoma a cellule squamose della testa e del collo |
|
E.1.1.1 | Medical condition in easily understood language |
Squamous cell carcinoma of the head and neck is a cancer that arises from particular cells called squamous cells and occurs within the head and neck region including the throat, mouth, and larynx. |
Il carcinoma a cellule squamose della testa e del collo è un cancro che nasce da cellule chiamate cellule squamose, si verifica nella regione della testa e del collo, compresa gola, bocca e laringe. |
|
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 atezolizumab plus tiragolumab and atezolizumab plus placebo on the basis of confirmed objective response rate. |
Valutazione dell'efficacia di atezolizumab più tiragolumab e atezolizumab più placebo, sulla base del tasso di risposta obiettiva |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo on the basis of duration of response, progression-free survival, overall survival, progression-free survival rate at 6 months, overall survival rate at 6 months and 12 months and time to confirmed deterioration in patient-reported physical functioning • To evaluate the safety of atezolizumab plus tiragolumab and atezolizumab plus placebo • To characterize the pharmacokinetics of atezolizumab and tiragolumab • To evaluate the immune response to atezolizumab and tiragolumab. |
• Valutare l'efficacia di atezolizumab più tiragolumab e atezolizumab più placebo, sulla base della durata della risposta, sopravvivenza libera da progressione, sopravvivenza complessiva, tasso di PFS a 6 mesi, tasso di OS a 6 mesi e a 12 mesi, tempo al deterioramento confermato del funzionamento fisico riportato dai pazienti • Valutare l'efficacia di atezolizumab più tiragolumab e atezolizumab più placebo • Caratterizzazione del profilo PK di atezolizumab e tiragolumab • Valutare la risposta immunitaria ad atezolizumab e tiragolumab |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age >= 18 years • Participants histologically or cytologically confirmed recurrent/metastatic SCCHN involving the oropharynx, oral cavity, larynx, or hypopharynx, that is considered incurable by local therapies • Known results from human papillomavirus status test for oropharyngeal carcinoma • No prior systemic therapy for metastatic and/or recurrent SCCHN • Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 • Tumor PD-L1 expression as determined by PD-L1 IHC assay in either a previously obtained archival tumor tissue or tissue obtained from a biopsy at prescreening/screening • Eastern Cooperative Oncology Group Performance Status of 0 or 1 • Adequate hematologic and end-organ function.
|
• Età >=18 anni • SCCHN ricorrente/metastatico confermato istologicamente o citologicamente, che interessa orofaringe, cavità orale, laringe o ipofaringe e che sia considerato incurabile con terapie locali • Risultati noti del test di determinazione dello stato di HPV per il carcinoma orofaringeo, • Nessuna terapia sistemica precedente per l'SCCHN metastatico e/o ricorrente • Malattia misurabile in base ai criteri RECIST v1.1 • Espressione di PD-L1 del tumore documentata mediante analisi centrale di un campione di tessuto tumorale rappresentativo, ottenuto dal tessuto tumorale conservato prelevato in precedenza o dal tessuto di una biopsia eseguita al prescreening/screening. • Performance status ECOG di 0 o 1 • Adeguata funzionalità ematologica e d'organo |
|
E.4 | Principal exclusion criteria |
• Progressive or recurrent disease within 6 months of the last dose of curative intent systemic treatment for locally advanced SCCHN • Grade >= 2 unresolved toxicity related to surgery or other prior therapies • Symptomatic, untreated, or actively progressing central nervous system metastases • History of leptomeningeal disease • 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 • History of additional malignancy other than SCCHN within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death • Severe infection within 4 weeks prior to initiation of study treatment • Current treatment with anti-viral therapy for HBV or HCV • 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 • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment. |
• Malattia in progressione o ricorrente entro 6 mesi dall'ultima dose di trattamento sistemico con intento curativo per SCCHN localmente avanzato • Tossicità di grado >=2 non risolta, correlata all'intervento chirurgico o ad altre terapie precedenti • Metastasi al sistema nervoso centrale (SNC) sintomatiche, non trattate o in progressione attiva • Anamnesi di malattia leptomeningea • Presenza in atto o anamnesi di malattia autoimmune o deficit immunitario • Anamnesi di fibrosi polmonare idiopatica, polmonite organizzativa, polmonite indotta da farmaco o polmonite idiopatica oppure evidenza di polmonite attiva • Anamnesi di neoplasia maligna diversa da SCCHN nei 5 anni precedenti alla randomizzazione, fatta eccezione per le neoplasie maligne con un rischio trascurabile di metastasi o decesso • Infezione grave nelle 4 settimane precedenti all'inizio del trattamento dello studio • Trattamento in corso con terapia antivirale per HBV o per HCV • Trattamento con una terapia sperimentale nei 28 giorni precedenti all'inizio del trattamento dello studio • Trattamento precedente con agonisti di CD137 o terapie che bloccano i checkpoint • Trattamento con agenti immunostimolatori sistemici nelle 4 settimane o nelle 5 emivite di eliminazione del farmaco precedenti all'inizio del trattamento dello studio • Trattamento con farmaci immunosoppressori sistemici nelle 2 settimane precedenti all'inizio del trattamento dello studio o previsione della necessità di farmaci immunosoppressori sistemici durante il trattamento dello studio |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Confirmed objective response rate |
Tasso di risposta obiettiva confermato |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 43 months |
1. Fino a 43 mesi |
|
E.5.2 | Secondary end point(s) |
1. Duration of Response 2. Progression free survival 3. Overall survival 4. Progression free survival rate at 6 months 5. Overall survival rate at 6 months and 12 months 6. Time to confirmed deterioration in patient-reported physical functioning 7. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 8. Serum concentration of atezolizumab and tiragolumab at specified timepoints 9. Prevalence of anti-drug antibodies (ADAs) to atezolizumab at baseline and during the study 10. Prevalence of ADAs to tiragolumab at baseline and during the study. |
1. Durata della 2. Sopravvivenza libera da progressione 3. Sopravvivenza complessiva 4. Tasso di PFS a 6 mesi 5. Tasso di OS a 6 mesi e a 12 mesi 6. Tempo al deterioramento confermato del funzionamento fisico riportato dai pazienti 7. Incidenza e gravità di eventi avversi, con la gravità determinata secondo la versione 5.0 dei criteri comuni di terminologia per gli eventi avversi del National Cancer Institute 8. Concentrazioni sieriche di atezolizumab e tiragolumab in determintati momenti temporali. 9. Prevalenza di anticorpi anti-farmaco al basale e incidenza di ADA anti-atezolizumab durante lo studio 10. Prevalenza di ADA anti-tiragolumab al basale e incidenza di ADA anti-tiragolumab durante lo studio |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-10. Up to 43 months |
1-10. fino a 43 mesi |
|
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 |
Immunogenicity |
Immunogenicità |
|
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Korea, Republic of |
New Zealand |
Taiwan |
Thailand |
United States |
France |
Greece |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
Czechia |
|
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
|
LVLS |
Ultima visita ultimo paziente |
|
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 | 43 |
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 | 43 |
E.8.9.2 | In all countries concerned by the trial days | 0 |