| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Squamous cell carcinoma of the head and neck |
|
| E.1.1.1 | Medical condition in easily understood language |
| Squamous cell carcinoma of the head and neck occurs in the outermost surface of the skin or certain tissues within the head and neck region including the throat, mouth, sinuses and nose. |
|
| 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 treatment based on pathologic complete response (pCR) as determined by central pathologic review |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of treatment based on pCR as determined by local pathologic review; pathologic response rate (pRR) and partial pathologic response (pPR) as determined by central pathologic review and local pathologic review, event-free survival (EFS), relapse-free survival (RFS), overall survival (OS) and objective response rate (ORR) according to RECIST v1.1.
• To evaluate the safety of treatment
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Age, >=18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histologically confirmed, resectable Stage III-IVA squamous cell carcinoma of the head and neck (SCCHN)
• Eligible candidate for R0 resection with curative intent at the time of screening
• Human papillomavirus (HPV)-negative test for oropharyngeal carcinoma, as determined locally by p16 immunohistochemistry (IHC), in situ hybridization, or polymerase chain reaction-based assay
• Measurable disease (at least one target lesion), as assessed according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Programmed death-ligand 1 (PD-L1) expression, defined as a combined positive score (CPS) >=1, as determined by a local or central laboratory through use of Dako PD-L1 IHC 22C3 pharmDx assay
• Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing
• Adequate hematologic and end-organ function
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV test at screening
• Negative hepatitis B surface antibody (HBsAb) and negative total hepatitis B core antibody (HBcAb) test at screening
• Negative hepatitis C virus (HCV) antibody test or positive HCV antibody test followed by a negative HCV RNA test at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse and donating eggs) or use contraceptive measures, as per protocol defined criteria
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as per protocol defined criteria |
|
| E.4 | Principal exclusion criteria |
• HPV-positive oropharyngeal cancer, as determined locally by p16 IHC, in situ hybridization, or by polymerase chain reactions-based assay
• Distantly metastasized SCCHN
• Any prior therapy for SCCHN, including immunotherapy, chemotherapy, or RT
• Prior treatment with any of the protocol-specified study treatments
• Treatment with investigational therapy within 42 days prior to initiation of study treatment
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Prior allogeneic stem cell or solid organ transplantation
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
• 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 on screening chest computed tomography (CT) scan
• History of malignancy other than SCCHN within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%)
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with therapeutic or prophylactic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment
• Significant cardiovascular disease such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure other than tumor resection, during the study
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, impair the ability of the patient to participate in the study, or renders the patient at high risk from treatment complications
• History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
• Known allergy or hypersensitivity to any of the study drugs or their excipients
• Known intolerance to any of the drugs required for premedication
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study
• Eligible only for the control arm
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. Pathologic complete response (pCR) as determined by central pathologic review |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. Up to approximately 5 years |
|
| E.5.2 | Secondary end point(s) |
1. Pathologic complete response (pCR) as determined by local pathologic review
2. Pathologic response rate (pRR) and partial pathologic response (pPR) as determined by central pathologic review and local pathologic review
3. Event-free survival (EFS)
4. Relapse-free survival (RFS)
5. Overall survival (OS)
6. Objective response rate (ORR) according to RECIST v1.1
Safety endpoints
7. Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0
8. Incidence and nature of Grade >=3 immune-related adverse events during the first 12 weeks
9. Rate and duration of delayed surgery due to treatment-related adverse events
10. Rate of surgical complications, as assessed according to the Clavien-Dindo surgical classification
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 1-10. Up to approximately 5 years |
|
| 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 | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Phase Ib/II multiple drug combination |
|
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 |
| Israel |
| Korea, Republic of |
| United States |
| France |
| Spain |
|
| 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
|
|
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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