E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Untreated unresectable or metastatic melanoma |
|
E.1.1.1 | Medical condition in easily understood language |
Untreated inoperable or metastatic melanoma |
|
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 | 10027481 |
E.1.2 | Term | Metastatic melanoma |
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 whether an investigational immunotherapy NKTR-214, when combined with nivolumab, is more effective than nivolumab by itself in participants with unresectable or metastatic melanoma that is previously untreated |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate efficacy of NKTR-214 combined
with nivolumab and that of nivolumab
monotherapy
- To evaluate the association between PD-L1
tumor expression on tumor cells (≥ 1% or < 1%/indeterminate) and efficacy measures
including PFS and ORR by BICR and OS.
-To evaluate the safety and tolerability of
NKTR-214 combined with nivolumab and
that of nivolumab monotherapy |
|
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 |
Intensive pharmacokinetics (PK)/biomarker sampling
It will be performed in approximately the first 45 randomized participants in order to have approximately 20 evaluable participants (18 years of age or older) in each arm to further characterize the PK / biomarker profile of the NKTR-214 and nivolumab combination in relation to nivolumab monotherapy. Evaluable participants are defined as participants who have samples collected to generate concentrationtime profiles that allow for PK analyses and computation of PK parameter values. Additional objectives of the study include characterization of safety and tolerability, as well as PK, potential redictive biomarkers, and changes in patient-reported outcomes for quality of life assessments.
Additional Research Collection - see protocol section 9.8.1
This protocol will include residual sample storage for additional research (AR). AR is optional for all study participants, except where retention and/or collection is prohibited by local laws or regulations, ethics committees, or institutional requirements.
This collection for additional research is intended to expand the translational R&D capability at Bristol-
Myers Squibb, and will support as yet undefined research aims that will advance our understanding of
disease and options for treatment. It may also be used to support health authority requests for analysis,
and advancement of pharmacodiagnostic development to better target drugs to the right patients. This
may also include genetic/genomic exploration aimed at exploring disease pathways, progression and
response to treatment etc. |
|
E.3 | Principal inclusion criteria |
- Eastern Cooperative Oncology Group (ECOG) performance status of </=1 (adults 18 years or older)/ Lansky Performance Score >/= 80% (minors ages 12-17 only)
- Histologically confirmed stage III (unresectable) or stage IV melenoma
- Treatment-naive participants (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma) with the exception of prior adjuvant treatment |
|
E.4 | Principal exclusion criteria |
- Active brain metastases or leptomeningeal metastases
- Uveal melanoma
- Participants with an active, known or suspected autoimmune disease |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Overall response rate (ORR) by Blinded Independent central review (BICR)
- Progression-free survival (PFS) by BICR
- Overall survival (OS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Clinical Benefit Rate (CBR) by BICR
- Duration of Response (DoR) by BICR
- Duration of overall Complete Response (DoCR) by BICR
- Time To Response (TTR) by BICR
- ORR by investigator
- PFS by investigator
- CBR by investigator
- DoR by investigator
- DoCR by investigator
- TTR by investigator
- PFS per BICR in biomarker population
- ORR per BICR in biomarker population
- OS in biomarker population
- Incidence of Adverse Events (AEs)
- Incidence of treatment-related AEs
- Incidence of Serious Adverse Events (SAEs)
- Incidence of treatment-related SAEs
- Incidence of laboratory abnormalities
|
|
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
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 |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Greece |
Ireland |
Israel |
Italy |
Netherlands |
New Zealand |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Switzerland |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |