E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor |
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E.1.1.1 | Medical condition in easily understood language |
Patients who had received prior immunotherapy treatment for specific type of head and neck cancer that has come back or spread to other parts of the body |
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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 | 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 |
To compare the effect of monalizumab and cetuximab (Arm A) relative to placebo and cetuximab (Arm B) in terms of overall survival (OS) in HPV-unrelated participants. |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of monalizumab and cetuximab (arm A) relative to placebo and cetuximab (arm B) by: 1. assessment of OS in all randomized participants; 2. assessment of PFS, ORR, DoR 3. assessment of disease-related symptoms, functioning and quality of life 4. characterization of the association between clinical outcome and protein expression in the tumor 5. assessment of safety and tolerability.
To investigate PK and immunogenicity of monalizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Are aged 18 years and over 2. Recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) 3. Received treatment using a PD-(L)1 inhibitor 4. Prior platinum failure 5. Received 1 or 2 prior systemic regimens for recurrent or metastatic SCCHN 6. At least one measurable lesion at baseline that qualifies RECIST 1.1 7. A fresh or recently acquired tumor tissue for the purpose of biomarker testing 8. WHO/ECOG PS of 0 or 1 |
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E.4 | Principal exclusion criteria |
1. Head and neck cancer of any primary anatomic location in the head and neck not specified in the inclusion criteria, including participants with SCCHN of unknown primary or non-squamous histologies 2. Had prior cetuximab therapy (unless it was administered in curative LA setting with radiotherapy and no disease progression for at least 6 months following the last cetuximab dose) 3. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis 4. Any concurrent anticancer treatment, except for hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival, defined as the time from the date of randomization until date of death due to any cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessments of survival status must be made periodically from enrollment. |
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E.5.2 | Secondary end point(s) |
- Overall survival, defined as the time from the date of randomization until date of death due to any cause.
- PFS is defined as time from randomization until disease progression, per RECIST 1.1 as assessed by the investigator at local site or death due to any cause, whichever occurs first.
- ORR is defined as the proportion of participants with measurable disease who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1.
- DoR is defined as the time from the date of first documented response until date of documented disease progression or death in the absence of disease progression.
- Patient questionnaires regarding wellbeing and symptom change in baseline scores across visits
- Concentration of monalizumab in the blood
- Presence of antibodies to monalizumab in the blood
- Measurement of specific biomarkers in the tumor sample(s)
- AEs, vital signs, clinical laboratory results, ECGs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Periodically from enrollment |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Peru |
Philippines |
Switzerland |
Korea, Democratic People's Republic of |
Taiwan |
Australia |
Brazil |
Canada |
Japan |
Russian Federation |
United Kingdom |
United States |
Austria |
Belgium |
Bulgaria |
France |
Germany |
Greece |
Italy |
Netherlands |
Poland |
Portugal |
Romania |
Spain |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |