E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent/metastatic head and neck squamous cell carcinoma. |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent/metastatic head and neck squamous cell carcinoma. |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071540 |
E.1.2 | Term | Head and neck 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 | 20.0 |
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) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck 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 compare the Progression Free Survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR) in first line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) subjects, treated with pembrolizumab monotherapy versus standard treatment 2) To compare PFS per RECIST 1.1 as assessed by BICR in first line R/M HNSCC subjects, treated with pembrolizumab in combination with chemotherapy versus standard treatment. 3) To evaluate the overall survival (OS) in first line R/M HNSCC subjects, treated with pembrolizumab monotherapy versus standard treatment. 4) To evaluate OS in first line R/M HNSCC subjects, treated with pembrolizumab in combination with chemotherapy versus standard treatment.
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E.2.2 | Secondary objectives of the trial |
1) To compare the Progression Free Survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR) in first line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) subjects, treated with pembrolizumab monotherapy versus standard treatment 2) To compare PFS per RECIST 1.1 as assessed by BICR in first line R/M HNSCC subjects, treated with pembrolizumab in combination with chemotherapy versus standard treatment. 3) To evaluate the overall survival (OS) in first line R/M HNSCC subjects, treated with pembrolizumab monotherapy versus standard treatment. 4) To evaluate OS in first line R/M HNSCC subjects, treated with pembrolizumab in combination with chemotherapy versus standard treatment. 5) To evaluate time to deterioration (TTD) in global health status/quality of life, pain and swallowing in first line R/M HNSCC subjects.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.
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E.3 | Principal inclusion criteria |
- Have histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapies. - Have measurable disease based on RECIST 1.1 as determined by the site. - Have a performance status of 0 or 1 on the ECOG Performance Scale. - Have results from local testing of HPV positivity for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cut off point. - Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy. Repeat samples may be required if adequate tissue is not provided. A newly obtained biopsy (within 90 days prior to start of study treatment) is strongly preferred, but an archival sample is acceptable.
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E.4 | Principal exclusion criteria |
- Has disease that is suitable for local therapy administered with curative intent. - Has progressive disease within six months of completion of curatively intended treatment for locoregionally advanced HNSCC. - Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or not fully recovered from AE due to previous treatment. - Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g. tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator. - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Corticosteroid use as pre-medication for allergic reactions (e.g. IV contrast), or as a prophylactic management of adverse events related to the chemotherapies specified in the protocol is allowed. - Has a known history of prior malignancy with recurrence in the last 5 years. - Active autoimmune disease that has required systemic treatment in past 2 years. - Has had an allogeneic tissue/solid organ transplan. - Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials. - Has an active infection requiring systemic therapy.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Progression-free survival (PFS) - RECIST 1.1 by BICR - Overall Survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Progression-free-survival is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. 2. Overall Survival is defined as the time from randomization to death due to any cause. Subjects without documented death at the time of the final analysis will be censored at the date of the last follow-up. |
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E.5.2 | Secondary end point(s) |
- Proportion progression free at 6 months and 12 months – RECIST 1.1 by BICR - Objective Response Rate (ORR) – RECIST 1.1 by BICR - Duration of Response (DOR) – RECIST 1.1 by BICR |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. The proportion progression free at 6 months and at 12 months is defined as the Kaplan-Meier estimate of the survival function for PFS at 6 months and 12 months, respectively. The progression-free status is based upon BICR per RECIST 1.1. 2. Objective response rate is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based upon BICR per RECIST 1.1. 3. For subjects who demonstrated CR or PR, duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first.
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
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 |
Argentina |
Australia |
Austria |
Brazil |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
Estonia |
Finland |
Germany |
Greece |
Hong Kong |
Hungary |
Israel |
Italy |
Japan |
Latvia |
Malaysia |
Mexico |
Netherlands |
Norway |
Peru |
Philippines |
Poland |
Russian Federation |
Singapore |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
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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 | |
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 |
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 |