E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Solid Tumors
Advanced B-cell NHL
|
|
E.1.1.1 | Medical condition in easily understood language |
Advanced Solid Tumors
Advanced B-cell NHL
|
|
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 | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025311 |
E.1.2 | Term | Lymphoma (non-Hodgkin's) |
E.1.2 | System Organ Class | 100000004864 |
|
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 this study is to determine which doses of urelumab and nivolumab are safe and tolerable when they are given together. |
|
E.2.2 | Secondary objectives of the trial |
Best Overall Response (BOR) Objective response rate (ORR), Duration of Response (DOR) Progression-free survival rate (PFSR).
Pharmacokinetics: Urelumab maximum concentration Cmax,(µg/mL), time to maximum concentration Tmax (hr), Area under the curve AUCTAU (µg.hr/mL), Area under the curve AUCinf (µg.hr/mL), Clearance (L/day), Volume of distribution (Vss), half life (t1/2), and trough concentration Cmin (µg/mL) will be evaluated using non compartmental analysis in all study subjects.
Immunogenicity: Occurrence of specific anti-drug antibodies (ADA) to urelumab and nivolumab, ADA status of the subject
|
|
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 - Number 01 - dated 9-Jul-14
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, CA186107
to study the association between genetic variation and drug response. |
|
E.3 | Principal inclusion criteria |
For Dose Escalation: Subjects with any previously treated advanced (metastatic or refractory) solid tumor type and B-cell non-Hodgkin lymphoma except subjects who have primary central nervous system tumors or with central nervous system metastases as the only site of active disease )
For Cohort Expansion: Subjects must have a previously treated advanced solid tumor or B cell non-Hodgkin’s lymphoma to be eligible:
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
For certain subjects, willing and able to provide pre-treatment and on-treatment fresh tumor biopsy
Women of child-bearing potential and men must use an acceptable method of contraception during treatment and for 23 weeks after treatment for women and 31 weeks for men.
|
|
E.4 | Principal exclusion criteria |
Known central nervous system metastases or central nervous system as the only source of disease
Other concomitant malignancies (with some exceptions per protocol)
Active, known or suspected autoimmune disease
Uncontrolled or significant cardiovascular disease
History of hepatitis (B or C)
History of active or latent tuberculosis.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety as measured by the rate of adverse events (AEs) and Serious Adverse Events (SAEs), is the primary endpoint of this Phase 1/2 study. All subjects who receive at least one (full or partial) dose of urelumab or nivolumab will be evaluated for safety during treatment and for up to 100 days in follow-up. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During treatment and first 100 days after treatment |
|
E.5.2 | Secondary end point(s) |
Best Overall Response (BOR) Objective response rate (ORR), Duration of Response (DOR) Progression-free survival rate (PFSR).
Pharmacokinetics: Urelumab maximum concentration Cmax,(µg/mL), time to maximum concentration Tmax (hr), Area under the curve AUCTAU (µg.hr/mL), Area under the curve AUCinf (µg.hr/mL), Clearance (L/day), Volume of distribution (Vss), half life (t1/2), and trough concentration Cmin (µg/mL) will be evaluated using non compartmental analysis in all study subjects.
Immunogenicity: Occurrence of specific anti-drug antibodies (ADA) to urelumab and nivolumab, ADA status of the subject
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
BOR, ORR, DOR, PFS: Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years
Pharmacokinetics:Time Frame: Cycles 1, 2, 3, 4, 6 and followup Days up to 100 days
Immunogenicity: Time Frame: Cycles 1 ,2, 3, 4, 6 and followup Days up to 100 days |
|
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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
A Phase 1/2 Dose Escalation and Cohort Expansion Study |
|
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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Canada |
France |
Germany |
Netherlands |
Spain |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 6 |