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). |
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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. |
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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 | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10082179 |
E.1.2 | Term | Squamous cell carcinoma of head and neck metastatic |
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 |
• To evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo on the basis of confirmed objective response rate. |
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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. |
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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.
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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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Confirmed objective response rate |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 |
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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) | 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 | 4 |
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 | 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 |
Korea, Republic of |
New Zealand |
Taiwan |
Thailand |
United States |
France |
Greece |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
Czechia |
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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 | |
E.8.9.1 | In the Member State concerned months | 43 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 43 |