E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous cell Non-small cell lung cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Squamous cell Non-small cell lung cancer |
|
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 | 17.0 |
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) |
|
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 compare the change in tumor size, and overall survival of BMS-936558 as compared with Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of prior platinum-based chemotherapy |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the ORR of BMS-936558 (nivolumab) versus docetaxel
2. To compare the progression-free survival (PFS) of BMS-936558 (nivolumab) versus docetaxel
3. To evaluate whether PD-L1 is a predictive biomarker for OS, ORR, or PFS.
4. To evaluate the proportion of subjects exhibiting disease-related symptom improvement by 12 weeks as measured by LCSS, in BMS-936558 (nivolumab) and docetaxel groups |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) men & women ≥ 18 years of age
2) Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease.)
3) Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
4) Measurable disease by CT/MRI per RECIST 1.1 criteria
5) ECOG performance status ≤ 1
6) An FFPE tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient. |
|
E.4 | Principal exclusion criteria |
1) Subjects with untreated CNS metastases are excluded. Subjects are eligible if CNS metastases are treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10mg daily prednisone (or equivalent)
2) Subjects with carcinomatous meningitis.
3) Subjects with active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
4) Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization.
5) Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
6) Prior treatment on the first line study CA184104 first line NSCLC study
7) Prior treatment with docetaxel
8) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
9) Treatment with any investigational agent within 14 days of first administration of study treatment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To compare the OS of BMS-936558 (nivolumab) versus docetaxel in
subjects with squamous cell NSCLC after failure of prior-platinum
doublet-based chemotherapy. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. To compare the ORR of BMS-936558 (nivolumab) versus docetaxel
2. To compare the progression-free survival (PFS) of BMS-936558
(nivolumab) versus docetaxel
3. To evaluate whether PD-L1 is a predictive biomarker for OS, ORR, or
PFS.
4. To evaluate the proportion of subjects exhibiting disease-related
symptom improvement by 12 weeks as measured by LCSS, in BMS-
936558 (nivolumab) and docetaxel groups |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Immunogenicity Assessments, Outcomes Research Assessments: Lung Cancer Symptom Scale (LCSS), and EuroPRO Group’s EQ-5D. |
|
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Austria |
Brazil |
Canada |
Chile |
Czech Republic |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Ireland |
Italy |
Mexico |
Netherlands |
Norway |
Peru |
Poland |
Romania |
Russian Federation |
Singapore |
South Africa |
Spain |
Turkey |
United Kingdom |
United States |
|
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
|
This study will end when analysis of survival is complete. All subjects will be followed for overall survival every 3 months until death, lost to follow-up, or withdrawal of study consent. The duration of study will be approximately 2 years (24 months). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |