E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Squamous cell Non-small cell lung cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Non-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 | 19.0 |
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 overall survival of BMS-936558 as compared with Docetaxel in subjects with non- 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 objective response rate (ORR) of BMS-936558 (nivolumab) to docetaxel
2. To compare progression-free survival (PFS) of BMS-936558 (nivolumab) to docetaxel
3. To evaluate whether PD-L1 expression is a predictive biomarker for OS and ORR
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 treatment groups
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Blood Sample Amendment 01 - Site Specific (version 1.0, dated 02-Jul-12) and Administrative Letter 01 (dated 14-Sep-2012)
The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA209057 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of non-squamous NSCLC Samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective. |
|
E.3 | Principal inclusion criteria |
1) Men & women ≥ 18 years of age
2) Subjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as second or third line of treatment for 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
Specific eligibility criteria for subjects originally randomized to the docetaxel arm B and now entering the nivolumab Extension Phase are included in the protocol in Section 3.1.3. |
|
E.4 | Principal exclusion criteria |
1) Subjects with untreated CNS metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or 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 1 diabetes mellitus, hypothyroidism only requiring skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment 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 with docetaxel
7) Treatment with any investigational agent within 14 days of first administration of study treatment.
Specific eligibility criteria for subjects originally randomized to the docetaxel arm B and now entering the nivolumab Extension Phase are included in the protocol in Section 3.1.3. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6, 12, 18, 24, 36, 48 months and 5 year |
|
E.5.2 | Secondary end point(s) |
1. To compare the objective response rate (ORR) of BMS-936558 (nivolumab) to docetaxel
2. To compare progression-free survival (PFS) of BMS-936558 (nivolumab) to docetaxel
3. To evaluate whether PD-L1 expression is a predictive biomarker for OS and ORR
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 treatment groups
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
6, 12, 18, 24, 36, 48 months and 5 year |
|
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: Peripheral Blood and Tumor Markers, Outcomes Research Assessments: Lung Cancer Symptom Scale (LCSS), and EuroPRO Group’s EQ-5D; Immunogenicity Assessments; Healthcare Resource Utilization data |
|
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
France |
Germany |
Hong Kong |
Hungary |
Italy |
Mexico |
Peru |
Poland |
Romania |
Russian Federation |
Singapore |
South Africa |
Spain |
Switzerland |
Turkey |
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
|
The 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 the study will be approximately 2.5 years (30 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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |