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 | 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 | 19.0 |
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 | 19.0 |
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 | 19.0 |
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 | 19.0 |
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 | 19.0 |
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.1.3 | 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, characterize the dose-limiting toxicities, and identify the maximum tolerated dose of BMS-986016 alone and in combination with nivolumab in subjects with select advanced (metastatic and/or unresectable) solid tumors and to provide preliminary information on the clinical benefits of the combination |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To characterize the pharmacokinetics (PK) of BMS-986016 administered alone and in combination with nivolumab.
- To investigate the preliminary overall response rate (ORR) and/ or disease control rate (DCR) of BMS-986016 administered alone and in combination with nivolumab in subjects with advanced solid tumors (Parts A)
- B Dose Escalation.To characterize the immunogenicity of BMS-986016 administered alone and in combination with nivolumab
- In Parts A and B, to assess the effect of BMS-986016 administered alone and in combination with nivolumab on QTc.
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E.2.3 | Trial contains a sub-study | No |
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 bladder 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 or 1
-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) |
Safety of BMS-986016 alone or in combination with nivolumab measured by the number of adverse events, deaths and laboratory abnormalities |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From first treatment dose (maximum of 2 years) and for up to 135 days after the last treatment dose.
Subjects who meet re-challenge criteria may be on treatment for up to an additional 2 years
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E.5.2 | Secondary end point(s) |
1/ Assess the effect of BMS-986016 administered alone or in combination with nivolumab on QTc
2/ Assess pharmacokinetics of BMS-986016 administered alone or in combination with nivolumab
3/ Assess preliminary efficacy of BMS-986016 administered alone or in combination with nivolumab
4/ Assess immunoginicity of BMS-986016 administered alone or in combination with nivolumab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ Pre-dose and 4 hours post-dose during Cycle 1 and Cycle 3, and at 30 days following the last dose of study drug per central reader assessments. Pre-dose for each cycle (up to 12 eight-week cycles) done locally
2/ Up to 1.8 years + 135 days post-treatment follow-up (total of up to approximately 2.3 years) The most frequent PK collections occur during Cycle 1 and Cycle 3: up to 15 timepoints over the 24 week period through Cycle 3.
3/ Week 8 of each cycle (up to 12 eight-week cycles) and at 30 days following the last dose of study drug for a total of up to approximately 2 years
Subjects who meet re-challenge criteria will continue efficacy assessments for up to an additonal 2 years
4/ Up to 1.8 years + 135 days post-treatment follow-up (total of up to approximately 2.3 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
| 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 | 15 |
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 |
Austria |
Denmark |
Finland |
France |
Germany |
Italy |
Netherlands |
Norway |
Spain |
Switzerland |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |