E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous cell non-small cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
Squamous cell non-small cell lung cancer |
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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 | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung 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 |
The purpose of the study is to assess the clinical activity of nivolumab, as measured by the independent radiology review committee (IRC) -assessed objective response rate (ORR), in subjects with advanced or metastatic squamous cell NSCLC who have progressed during or after both platinum doublet based chemotherapy and at least one additional systemic therapy |
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E.2.2 | Secondary objectives of the trial |
To estimate the ORR based on investigator assessment of response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Men and Women ≥ 18 years of age
2) Subjects with histologically- or cytologically-documented squamouscell NSCLC who present with Stage IIIB/ Stage IV disease (according to version 7 of the International Association for the Study of
Lung Cancer Staging Manual in Thoracic Oncology), or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease).
3) Subjects must have experienced disease progression or recurrence after both a platinum doublet based chemotherapy regimen and at least one additional systemic therapy.
i) Additional therapies are defined as follows:
- Agents that are FDA- or EMA-approved for use after a prior regimen, given as monotherapy or in combination; or
- Vinorelbine- or gemcitabine-containing regimens given as part of locally accepted standard-of-care, for subjects who are not candidates for docetaxel.
ii) Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy.
iii) Prior platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease is considered first-line therapy only if recurrent (local or metastatic) disease
developed within 6 months of completing therapy. Subjects with recurrent disease > 6 months must also have progressed after a subsequent platinum-based regimen given to treat the recurrence.
iv) Subjects with activating EGFR mutations may have received an EGFR tyrosine kinase inhibitor prior to platinum-based chemotherapy.
4) Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria; radiographic tumor assessment performed within 28 days of first dose of study drug.
Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
5) Eastern Cooperative Oncology Arm (ECOG) performance status of 0 or 1 |
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E.4 | Principal exclusion criteria |
1) Subjects with active CNS metastases are excluded. MRI of the brain should be performed in all patients at screening. Subjects are eligible if CNS metastases are adequately treated, and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrolment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent). Subjects with brain metastases eligible for the study will have an obligatory brain MRI on a regular basis during the study in order to confirm their brain metastases status.
2) Subjects with carcinomatous meningitis.
3) Active known or suspected autoimmune disease or subjects with interstitial lung disease.
4) Prior treatment on either arm of study CA209017 or CA184104.
5) Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
6) Subjects with a condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is IRC-assessed ORR |
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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) |
The secondary endpoint is Investigator-assessed ORR. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity Assessments (Anti-Drug Antibody), Biomarker Assessments |
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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 | No |
E.8.1.1 | Randomised | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
France |
Germany |
Italy |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 15 |