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 | 20.0 |
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 1 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; minimum of 242 screened subjects. The Scientific
Steering Committee will provide guidance and scientific expertise on the risk/benefit ratio 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. A fresh biopsy is not required to take part in the study.
c) Subjects must have experienced disease recurrence or progression during or after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease.
i) Maintenance therapy following platinum doublet-based
chemotherapy is not considered as a separate regimen of therapy
ii) Subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible.
iii) Subjects with recurrent disease > 6 months after platinumcontaining adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence, are eligible.
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 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)
Age and Reproductive Status
a) Males and Females, ages 18 or older
b) Women of childbearing potential (WOCBP) must have a negative
serum or urine pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of HCG) within 24 hours prior to the start of study drug
c) Women must not be breastfeeding
d) WOCBP must agree to follow instructions for method(s) of
contraception for the duration
of treatment with nivolumab plus approximately 5 half-lives of
nivolumab plus 30 days (duration of ovulatory cycle) for a total of 5
months post-treatment completion.
e) Males who are sexually active with WOCBP must agree to follow
instructions for method(s) of contraception for the duration of treatment
with nivolumab plus approximately 5 half-lives of the study drug plus 90
days (duration of sperm turnover) for a total of 7 months post-treatment
completion.
f) Azoospermic males and WOCBP who are continuously not
heterosexually active are exempt from contraceptive requirements.
However, they must still undergo pregnancy testing as described in this
section. |
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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 ), 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
• 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 | 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.8.2.4 | 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 | 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 |
Denmark |
Finland |
Greece |
Hungary |
Ireland |
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 |