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 | 9 |
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 |
Australia |
Brazil |
Canada |
Japan |
Korea, Democratic People's Republic of |
Peru |
Philippines |
Russian Federation |
Taiwan |
United States |
Austria |
Belgium |
France |
Germany |
Greece |
Italy |
Poland |
Portugal |
United Kingdom |
Bulgaria |
Netherlands |
Romania |
Spain |
Switzerland |
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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 | |
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 |