E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
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 |
To assess the safety and tolerability of BMS-986148 administered as monotherapy and in combination with nivolumab in subjects with select advanced solid tumors. |
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E.2.2 | Secondary objectives of the trial |
1- To assess the preliminary anti-tumor activity of BMS-986148 as monotherapy and in combination with nivolumab as measured by objective response rate (ORR), response duration, and progression-free survival (PFS)
2- To characterize the PK of the total antibody (unconjugated antibody + antibody conjugated to tubulysin or
antibody conjugated to any tubulysin metabolites), active anti-drug conjugate (ADC, antibody conjugated
to tubulysin), and unconjugated tubulysin when BMS-986148 is administered as monotherapy and in
combination with nivolumab
3- To characterize the PK of nivolumab when administered in combination with BMS-986148
4- To assess the effect of BMS-986148 monotherapy dosage regimen and exposure (active ADC and unconjugated tubulysin) on the QT interval
5- To characterize the immunogenicity of BMS-986148 as monotherapy and in combination with nivolumab
6- To characterize the immunogenicity of nivolumab in combination with BMS-986148 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must have pancreatic, ovarian, gastric, non-small cell cancer or mesothelioma. For dose expansion, must have tumor that is positive for mesothelin
• Expected to have life expectancy of at least 3 months
• Men and women 18 years old or older
• Must have measurable tumor per Response Evaluation Criteria In Solid Tumors (RECIST) or modified RECIST for malignant pleural mesothelioma
• ECOG of 0 to 1 |
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E.4 | Principal exclusion criteria |
• Cancer metastases in the brain
• Moderate eye disorders
• Active infection or past hepatitis B or C infection
• Major surgery less than 1 month before the start of the study
• Uncontrolled heart disease
• Impaired liver or bone marrow function
• For Part 3 only : Active, known, or suspected autoimmune disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of AEs at worst grade, serious AEs (SAEs) at worst grade, AEs leading to discontinuations, deaths and frequency of laboratory test toxicity grade shifting from baseline. Safety will be evaluated from the time that the subject signs the informed consent, and for up to 60 days (or 100 days for combination therapy) after the last dose of study drug. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From the time that the subject signs the informed consent, and for up to 60 days (or 100 days for combination therapy) after the last dose of study drug. |
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E.5.2 | Secondary end point(s) |
Pharmacokinetic: Select PK parameters including Cmax, Tmax, AUC(0-t), AUC(TAU), Ctau, Ctrough, CLT, Vss, Vz, AI_AUC, AI_Cmax, AI_Ctau, Cavg, and T-HALF will be assessed from serum and plasma concentration-time data collected during Cycle 1 and Cycle 4.
Efficacy: BOR, ORR, duration of response, PFS rate at select times (overall survival rate at select times is an exploratory efficacy endpoint).
Immunogenicity: Frequency of subject immunogenicity status.
Electrocardiography (ECG): Changes in QTcF (ΔQTcF) from baseline at selected times. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic: Day 1 to Day 84 for Q3W and Day 1 to 11 for 2Q1W
Efficacy: Approximately 5 years
Immunogenicity: Day 1 - 60 days after the last dose of BMS-986148
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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/IIa: FIH and Dose Escalation |
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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 | Yes |
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 | 5 |
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 | 9 |
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 |
Belgium |
Canada |
Japan |
Korea, Republic of |
Netherlands |
Singapore |
Spain |
United Kingdom |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |