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 | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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 of lirilumab (BMS-986015) given in combination with nivolumab (BMS-936558) and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination, in subjects with advanced (metastatic and/or unresectable) solid tumors.
-) To assess the preliminary anti-tumor activity of the combination of lirilumab (BMS 986015) and nivolumab (BMS-936558) in subjects with advanced solid tumors. |
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E.2.2 | Secondary objectives of the trial |
-) To characterize the pharmacokinetics (PK) of lirilumab (BMS-986015) and nivolumab (BMS-936558) when co-administered.
-) To monitor immunogenicity of lirilumab (BMS-986015) and nivolumab
(BMS-936558) administered as combination therapy.
-) To assess the pharmacodynamic effect in tumor tissue on tumor infiltrating lymphocyte (TIL) subsets from melanoma (MEL), and head and neck squamous cell carcinoma (SCCHN) subjects treated with lirilumab (BMS-986015) given in combination with nivolumab (BMS-936558). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent
2) Target Population
a) Subjects must have histologic or cytologic confirmation of a solid malignancy that is advanced (metastatic and/or unresectable):for Cohort Expansion part 2
Head and Neck Squamous Cell Carcinoma (SCCHN) (oral cavity, pharynx, larynx)
ii. Subjects must have ≤ 5 prior treatment regimens. The following are not considered separate lines of treatment: addition of a compound to an on-going regimen, re-starting the same regimen after a drug holiday, or switching from intravenous to oral therapy
b) Presence of at least one lesion with measurable disease as defined by RECIST v1.1
criteria for response assessment.
c) ECOG status of 0 or 1.
fd Life expectancy of ≥ 12 weeks.
3) Age, Sex, and Reproductive Status
a) Men and women, ages > 18. |
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E.4 | Principal exclusion criteria |
1) Target Disease Exceptions
2) Medical History and Concurrent Diseases
a. Subjects with a prior malignancy are excluded, except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, localized prostate cancer, carcinoma in situ of the cervix, or in situ ductal or lobular carcinoma of the breast.
b. Subjects with any active autoimmune disease or history of known or suspected autoimmune disease, with the exception of subjects with isolated vitiligo, resolved childhood asthma/atopy, and controlled thyroid disorders.
3) Prohibited Prior Treatments and/or Therapies
a. Prior therapy with an anti-KIR, anti-PD-1, or anti-PD-L1, antibody.
b. Prior treatment regimens with any immune cell modulating antibody such as anti-CD137 and anti-OX40.
c. Exposure to any other investigational drug within 4 weeks prior to the first dose of study drug (within 101 days for anti-CTLA4 therapy).
d. Any anti-cancer therapy (e.g., chemotherapy, biologics, vaccines, radiotherapy with curative intent, or hormonal treatment) within 4 weeks prior to the first dose of study drug administration (within 101 days for anti-CTLA4 therapy), with the exception of GnRH agonist therapy for subjects with prostate cancer.
4) Physical and Laboratory Test Findings
5) Sex and Reproductive Status
a) Women who are pregnant or are breastfeeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety is the primary endpoint in this Phase I/II study.
The primary objective (to assess the safety and tolerability of lirilumab (BMS-986015) given in combination with nivolumab (BMS-936558) and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination) will be measured by the following
primary endpoints:
a) Incidence of adverse events.
b) Incidence of clinical laboratory test abnormalities including hematology and serum chemistry, and thyroid panel abnormalities. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Incidence of adverse events will be collected from Day 1 until 100 days after the subject’s last dose of study drug or until they discontinue the study as per protocol.
Incidence of clinical laboratory test abnormalities will be assessed at specified time points as designated in the Time and Events Section (5.1) of the protocol. |
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E.5.2 | Secondary end point(s) |
Efficacy endpoint:
The secondary objective of assessing preliminary anti-tumor activity will be based on endpoints
described below using RECIST v1.1:
1) Best overall response (BOR) is the best response designation recorded from the start of the
study treatment until the end of treatment taking into account any requirement for confirmation,
based on RECIST v1.1 criteria.
2) Objective response rate (ORR) is defined as the total number of subjects whose BOR is either
CR or PR divided by the total number of subjects in the population of interest.
3) Duration of Response (DOR)
4) Progression-Free Survival Rate (PFSR) is defined as the probability of a subject remaining
progression-free and surviving to 24 weeks
Pharmacokinetics (PK)
Immunogenicity
Biomarkers |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
BOR will be determined based on tumor measurements occurring every 8 weeks during the Treatment period (Cycle 1 Day 1 through Cycle 12 Day 56), and once during the Clinical Follow-up period.
DOR defined as the number of days between the date of first response and the subsequent date of objectively documented disease progression based on the criteria (RECIST v1.1) or death
PFSR is 24 weeks
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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 | Yes |
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 | 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 | 1 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 26 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 18 |