E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Squamous Cell (Sq) Non-Small Cell Lung Cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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 determine the incidence of high-grade (CTCAE v4.0 Grades 3-4), treatment-related, select adverse events in subjects with advanced or metastatic SqNSCLC who progressed during or after at least 2 systemic therapies. |
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E.2.2 | Secondary objectives of the trial |
• To determine the incidence and to characterize the outcome of all high-grade (CTCAE v4.0 Grades 3-4), select adverse events in subjects with advanced or metastatic SqNSCLC who have progressed during or after at least 2 prior systemic therapies and are treated with nivolumab monotherapy
• To estimate overall survival (OS) in all treated subjects
• To estimate investigator-assessed objective response rate (ORR)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria
a) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS):
i) PS 0 to 1 (Subgroup1)
ii) PS 2 (Subgroup 2; maximum of 300 subjects; clinical risk/benefit ratio will be monitored by the Scientific Steering Committee following a Safety Management Plan
b) Subjects with histologically or cytologically-documented SqNSCLC who presented with stage IIIb/stage IV disease or who developed recurrent or progressive disease following prior definitive therapy for localized or local advanced disease. Enrollees must not be eligible for another clinical study with nivolumab. A fresh biopsy is not required to take part in the study.
c) Subjects must have experienced disease progression or recurrence during or after both a platinum doublet-based chemotherapy regimen and at least 1 additional systemic therapy
i) Additional systemic therapies are defined as agents that are locally accepted and established for use as monotherapy or in combination for the treatment of stage IIIb/stage IV SqNSCLC.
ii) Experimental therapies when given as a separate regimen are considered as separate lines of therapy.
iii) Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate line of therapy.
iv) 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) or progressive disease developed within 6 months of completing therapy. Subjects with recurrent disease > 6 months must also have progressed during or after at least 2 subsequent regimens (a platinum doublet-based chemotherapy regimen and at least 1 additional systemic therapy OR at least 2 additional systemic therapies) given to treat the recurrence
d) Subjects with CNS metastases:
i) Subjects are eligible if CNS metastases are 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 first dose. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of < or = 10 mg daily prednisone (or equivalent)
OR
ii) Subjects are eligible if they have previously untreated CNS metastases that are neurologically asymptomatic. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of < or = 10 mg daily prednisone (or equivalent)
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E.4 | Principal exclusion criteria |
Key exclusion criteria:
a) Subjects with untreated, symptomatic CNS metastases are excluded
b) Subjects with carcinomatous meningitis are excluded.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of high-grade (CTCAE v4.0 Grades 3-4 or higher), treatment-related, select adverse events
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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 endpoints include:
• Incidence of high grade (Grade 3-4) select adverse events
• Median time to onset and median time to resolution (Grades 3-4) of select adverse events
• OS is defined as the time from first dosing date to the date of death. A subject who has not died will be censored at last known date alive. OS will be followed continuously while subjects are on treatment and every 3 months via in-person or phone contact after subjects discontinue the study drug.
• ORR is defined as the number and percentage of subjects with a best overall response (BOR) of confirmed CR or PR. ORR as assessed by the investigator will be reported.
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 195 |
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 |
Austria |
Belgium |
Bulgaria |
Croatia |
Czech Republic |
Denmark |
Finland |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Lithuania |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |