E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic solid tumors:
1) Triple Negative Breast Cancer (TNBC)
2) Gastric Cancer (GC)
3) Pancreatic Cancer (PC)
4) Small Cell Lung Cancer (SCLC). |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced or metastatic solid tumors:
1) Triple Negative Breast Cancer (TNBC)
2) Gastric Cancer (GC)
3) Pancreatic Cancer (PC)
4) Small Cell Lung Cancer (SCLC). |
|
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041067 |
E.1.2 | Term | Small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast 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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the safety and efficacy of nivolumab as a single agent or in combination with ipilimumab in 4 tumor types - triple-negative breast cancer (TNBC), gastric cancer (GC), pancreatic adenocarcinoma (PC), and small cell lung cancer (SCLC). |
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E.2.2 | Secondary objectives of the trial |
• BOR (Best Overall Response)
• DOR (Duration of Response)
• Safety
• PFS (Performance Free Survival)
• OS (Overall Survival) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects with histologically confirmed locally advanced or metastatic disease of the following tumor types:
◦ Triple Negative Breast Cancer
◦ Gastric Cancer
◦ Pancreatic Cancer
◦ Small Cell Lung Cancer
• Subjects must have measurable disease
• ECOG of 0 or 1. |
|
E.4 | Principal exclusion criteria |
Exclusion
• Active brain metastases or leptomeningeal metastases.
• Subjects with active, known or suspected autoimmune disease.
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
• Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including ipilimumab; or other medicines specifically targeting T cell is also prohibited. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) in all assigned subjects as determined by the investigators. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of assigned subjects |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up until time of first documented tumor progression or death (approximately up to 17 months) |
|
E.5.2 | Secondary end point(s) |
Rate of treatment-related adverse events (AEs) leading to drug discontinuations during the first 12 weeks of treatment |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to Week 12 of treatment |
|
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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers assessments, Outcomes Research assessments, Immunogenicity Assessments |
|
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 |
Phase I/II signal detection study to determine safety and efficacy in the 4 selected tumor types |
|
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
option to cross over from Nivo to Nivo/ipi combination for those that progress on monotherapy arm |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
each arm in each tumor type will be evaluated independently |
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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 | 12 |
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 |
Finland |
Germany |
Italy |
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
|
The study will end once survival follow-up has concluded |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 14 |