E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Malignant Tumors |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Malignant Tumors |
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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 | 10048683 |
E.1.2 | Term | Advanced cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Part 1: Dose Escalation:
To determine the safety, tolerability, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD)/maximum administered dose (MAD)/alternate dose(s) of BMS-986205 administered as monotherapy and in combination with nivolumab in subjects with advanced malignant tumors.
Part 2: Dose Expansion:
To investigate the anti-tumor activity of BMS-986205 administered in combination with nivolumab in distinct cohorts of subjects with advanced malignant tumors.
To evaluate the safety and tolerability of BMS-986205 in combination with nivolumab in subjects with advanced malignant tumors.
Part 3: BMS-986205, Nivolumab and Ipilimumab Combination
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and preliminary anti-tumor activity of BMS-986205 administered in combination with both nivolumab and ipilimumab in subjects with select advanced malignant tumors.
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E.2.2 | Secondary objectives of the trial |
- To characterize the pharmacokinetics (PK) of BMS-986205 administered alone, in combination with nivolumab, and in combination with both nivolumab and ipilimumab.
- To investigate the anti-tumor activity of BMS-986205 administered in combination with nivolumab in dose escalation and clinical pharmacology substudies.
- To characterize the pharmacodynamic activity of BMS-986205 administered alone, in combination with nivolumab, and in combination with both nivolumab and ipilimumab.
- To characterize the immunogenicity of nivolumab when administered in combination with BMS-986205 and in combination with both BMS-986205 and ipilimumab.
- To characterize the immunogenicity of ipilimumab when administered in combination with nivolumab and BMS-986205
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• During dose escalation, subjects with advanced solid tumors that have progressed following at least one standard regimen
• During cohort expansion, subjects with various solid tumors that either have received at least one prior therapy or are treatment naive, depending on the specified tumor type
• Subjects must have measurable disease
• Subject must consent to provide previously collected tumor tissue and must consent to a repeat tumor biopsy during screening.
• Women and men ≥18 years of age with performance status of 0 or 1
• At least 4 weeks since any previous treatment for cancer
• Must be able to swallow pills or capsules
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
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E.4 | Principal exclusion criteria |
• Active or chronic autoimmune diseases
• Uncontrolled or significant cardiovascular disease
• Chronic hepatitis
Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)Other protocol defined inclusion/exclusion criteria could apply
• Uncontrolled or significant cardiovascular disease
• Active infection
• History of any chronic Hepatitis, active Hepatitis B or C, human immunodeficiency virus(HIV), or acquired immune deficiency syndrome(AIDS)
• Active Central nervous system (CNS) metastases and CNS metastases as the only sites of disease
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E.5 End points |
E.5.1 | Primary end point(s) |
1/ Safety and tolerability of BMS-986205 as measured by incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities.
2/ Safety of BMS-986205 plus nivolumab as measured by incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities.
3/ Safety of BMS-986205 plus both nivolumab and ipilimumab as measured by incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities.
4/ Anti-tumor activity of BMS 986205 administered in combination iwth nivolumab as measured by the best overall response (BOR), duration of response (DOR), and progression-free survival rates (PFSRs) at multiple time points
5/ Anti-tumor activity of BMS 986205 administered in combination with both nivolumab and ipilimumab as measured by the best overall response (BOR), duration of response (DOR), and progression-free survival rates (PFSRs) at multiple time points
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1/ [Time Frame: 100 days after the last dose of study therapy]
2/ [Time Frame: 100 days after the last dose of study therapy]
3/ [Time Frame: 100 days after the last dose of study therapy]
4/ [Time Frame: Approximately 3 years]
5/ [Time Frame: Approximately 3 years]
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E.5.2 | Secondary end point(s) |
A/ To characterize the PK and PD of BMS-986205 administered alone, in combination with nivolumab, and in combination with both nivolumab and ipilimumab.
1. Maximum observed plasma concentration (Cmax) of BMS-986205 [Time Frame: Approximately 3 years]
2. Time of maximum observed plasma concentration (Tmax) of BMS-986205 [Time Frame: Approximately 3 years]
3. Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986205 [Time Frame: Approximately 3 years]
4. Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-986205 [Time Frame: Approximately 3 years]
5. Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-986205 [Time Frame: Approximately 3 years]
6. Trough observed plasma concentration at the end of the dosing interval (Ctrough) of BMS-986205 [Time Frame: Approximately 3 years]
7. Observed plasma concentration at 24 hours (C24) of BMS-986205 [Time Frame: Approximately 3 years]
8. Apparent terminal phase half-life (T-HALF) of BMS-986205 [Time Frame: Approximately 3 years]
9. Apparent total body clearance (CLT/F) of BMS-986205 [Time Frame: Approximately 3 years]
10. Apparent renal clearance (CLR/F) of BMS-986205 [Time Frame: Approximately 3 years]
11. Volume of distribution of terminal phase (Vz/F) of BMS-986205 [Time Frame: Approximately 3 years]
12. Apparent volume of distribution at steady state (Vss/F) of BMS-986205 [Time Frame: Approximately 3 years]
13. Accumulation index (AI) of BMS-986205 [Time Frame: Approximately 3 years]
14. Percent urinary recovery (%UR) of BMS-986205 [Time Frame: Approximately 3 years]
15. Percent urinary recovery over 24 hours(%UR24) of BMS-986205 [Time Frame: Approximately 3 years]
16. Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMS-986205 [Time Frame: Approximately 3 years]
17. Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight (single dose in clinical pharmacology substudy only) [MR_AUC(0-T)] of BMS-986205 [Time Frame: Approximately 3 years]
18. Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMS-986205 [Time Frame: Approximately 3 years]
19. Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight (single dose in clinical pharmacology substudy only) [MR_AUC(INF)] of BMS-986205 [Time Frame: Approximately 3 years]
20. Anti-drug antibody (ADA) response to Nivolumab in combination with BMS-986205 [Time Frame: Approximately 3 years]
B/ To characterize the immunogenicity of nivolumab when administered in combination with BMS-986205 and in combination with both BMS-986205 and ipilimumab.
C/ To characterize the immunogenicity of ipilimumab when administered in combination with nivolumab and BMS-986205
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
[Time Frame: Approximately 3 years] |
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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 | Yes |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | 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 | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 23 |
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 |
Australia |
Canada |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
United States |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 5 |