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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
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) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067946 |
E.1.2 | Term | Renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 A+B+A1:to assess safety,tolerability,DLTs,MTD of BMS986016 alone &in combo with nivo (advanced solid tumors); to gather preliminary efficacy information of BMS986016 alone Part C:to further establish safety&tolerability of BMS986016 + nivo administered sequentially; to investigate the preliminary efficacy of BMS986016 in combo with nivo as measured by ORR, DCR,DOR (multiple tumor types) Part D: to assess safety&tolerability of more convenient dosing regimen;Part D1-Q2W: to demonstrate preliminary clinical evidence of the treatment effect,measured by ORR,as determined by BICR using RECIST v1.1 (advanced melanoma);Part D1-Q4W: to confirm with Q4W dosing of BMS986016 160 mg in combo with nivo480 mg,the safety&efficacy of the Q2W dosing of BMS986016 80 mg in combo with nivo 240mg (advanced melanoma) Part E: to demonstrate that 480 mg BMS986016 +480 mg nivo Q4W provides significantly greater clin benefit (increased ORR) vs 160mg BMS 986016+480 mg nivoQ4W dose (melanoma) |
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E.2.2 | Secondary objectives of the trial |
-To characterize PK of BMS986016 alone and with nivo -To investigate preliminary ORR and/or DCR of BMS986016 alone and with nivo in subjects with advanced solid tumors(A,B,Dose Esc) -To characterize immunogenicity of BMS986016 alone and with nivo -To assess effect of BMS986016 alone & with nivo on QTc(A,B) -To evaluate DOR, DCR, PFS rates at pre-specified time points based on BICR assessments using RECISTv1.1 in advanced melanoma subjects i)with, i)with a lack, i)regardless LAG-3 expression(D1, D2) -To evaluate ORR, DCR, DOR, PFS rates at pre-specified time points based on Investigator assessments using RECISTv1.1 in advanced melanoma subjects i)with, i)with a lack, i)regardless LAG-3 expression(D1,D2) -To assess the 1Y and 2Y landmark OS in advanced melanoma subjects(D1, D2) -To assess safety and tolerability of more convenient dosing regimen in advanced melanoma subjects(D2) -To evaluate clinical benefit of 480mg BMS986016 + 480mg nivo Q4W using DOR in melanoma subjects(E)
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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 |
For details, see protocol Section 5.7.11 Additional Research Collection |
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E.3 | Principal inclusion criteria |
-For Dose escalation: subjects with cervical, ovarian, bladder and CRC, head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and NSCLC; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with/out anti-CTLA-4. -For Dose Expansion: all of the above in escalation except for cervical, ovarian and CRC -Progressed, or been intolerant to, at least one standard treatment regimen -Received any number of prior treatment regimens -ECOG performance status of 0 to 2 -At least 1 lesion with measurable disease at baseline -Availability of an existing tumor biopsy sample (or consent to allow pre-treatment tumor biopsy if sample not available)
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E.4 | Principal exclusion criteria |
- Primary CNS tumors or solid tumors with CNS metastases as the only site of active disease - Autoimmune disease - Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent - Uncontrolled CNS metastases |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Proportion of subjects with Adverse Events (AEs) - Proportion of subjects with Serious Adverse Events (SAEs) - Proportion of Deaths - Proportion of subjects with laboratory abnormalities in blood - Proportion of subjects with laboratory abnormalities in blood serum - Proportion of subjects with laboratory abnormalities in urine - Objective response rate (ORR) - Disease control rate (DCR) - Duration of response (DOR) - Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ - Proportion of subjects with AEs leading to discontinuation of treatment
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately Up to 3 years Approximately Up to 3 years Approximately Up to 3 years Approximately Up to 3 years Approximately Up to 3 years Approximately Up to 3 years Approximately 3 years Approximately 3 years Approximately 3 years Approximately 3 years Approximately Up to 3 years
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E.5.2 | Secondary end point(s) |
- Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab - Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab - Concentration at the end of a dosing interval (Ctau) [Eg: concentration at 336 hours] of BMS-986016 administered both alone and in combination with nivolumab - Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab - Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab - Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab - Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff AUC) of BMS- 986016 administered both alone and in combination with nivolumab - Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Accumulation index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016 administered both alone and in combination with nivolumab - Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016 administered both alone and in combination with nivolumab - Degree of fluctuation (DF) or fluctuation index ([Cmax -Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab - Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab - QTc interval from centrally read electrocardiograms (ECGs) - Best overall response (BOR) - Objective response rate (ORR) - Disease control rate (DCR) - Duration of response (DOR) - Progression-free survival (PFS) rates - Overall survival (OS) - Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 2.3 years - Approximately 3 years - Approximately 3 years - Approximately 3 years - Approximately 3 years - Up to approximatively 3 years - Approximately 2 years - 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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Dose Escalation and Cohort Expansion Study (Safety, Tolerability, and Efficacy) |
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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 | 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 | 26 |
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 |
Switzerland |
Australia |
Canada |
Japan |
United Kingdom |
United States |
Austria |
Denmark |
Finland |
France |
Germany |
Italy |
Netherlands |
Norway |
Spain |
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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 | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 12 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 20 |