all solid tumors in part 1 and only NSCLC, RCC, CRPC, SCCHN, melanoma and pancreatic cancer in part 2. advanced solid tumors cancer
Conditions
Interventions
The medical intervention in this study is BMS-986179 alone or in combination
with Nivolumab. Both drugs are supplied as a liquid. BMS-986179 has a strength
of 350mg/vial and Nivolumab with a strengt
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Signed informed consent including consent for submission of a fresh tumor sample (and if available archival). At least 18 years old and have histological or cytological confirmation of a malignancy that is advanced (metastatic and unresectable) with measureable disease and have at least 1 lesion that is biopsy-accessible. For parts 1A and 1B Subjects must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting, if such a therapy exists. Subjects who refuse or are ineligible for standard therapy will be allowed to enroll provided their refusal/ineligibility is documented in medical records All solid tumor histologies will be permitted except for subjects with primary CNS tumors or with CNS metastases as the only site of active disease. For Part 2 Subjects must have either NSCLC, RCC, CRPC, SCCHN, melanoma or pancreatic cancer. Subjects must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen. All Subjects Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of * 1. Subjects who have prior exposure to any agent specifically targeting checkpoint pathway inhibition or any agent specifically targeting T-cell co-stimulation pathways are permitted after at least a 4 week washout period. Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose of the study drug. Subjects must have adequate organ function Ability to comply with treatment, PK, immunogenicity, biomarker, and PD sample collection, and required study follow-up.
Exclusion criteria
Exclusion criteria: Subjects with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded. Subjects with carcinomatous meningitis are excluded Subjects who have participated in any prior clinical study with nivolumab in which OS is listed as the primary or co primary endpoint and which has not completed analysis based on the primary endpoint are excluded. For subjects with pancreatic cancer those subjects with clinically relevant ascites at baseline or with moderate radiographic ascites are excluded. Subjects with a prior malignancy, different from the one used for enrolment in this study, diagnosed less than 2 years ago are excluded. Any anti-cancer therapy within 4 weeks of the start of study drug Subjects who have received prior therapy with an anti-CD73 antibody, an anti-CD39 antibody, or an adenosine 2A receptor inhibitor are excluded Subjects with active, known or suspected autoimmune disease. Subjects with interstitial lung disease or chronic obstructive pulmonary disease Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications Subjects with uncontrolled or significant cardiovascular disease Subjects with active hepatitis, active bacterial, viral, or fungal infections, a known history of testing positive for human immunodeficiency virus (HIV) Subjects who have undergone any major surgery within 4 weeks of study drug administration are excluded Subjects with a history of any significant drug allergy or ongoing adverse events.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Outcome Measures: Safety assessment will be based on comprehensive medical review of adverse events, vital signs, ECGs, physical examinations and the results of laboratory tests. Adverse events will be assessed continuously during the study and for 100 days after the last treatment The incidence of observed adverse events will be tabulated and reviewed for potential significance and clinical importance. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic Measures: PD effect of CD73 inhibition will be measured by CD73 enzyme assays and pre and on treatment tumor biopsies. Pharmacokinetic Measures: Serial serum samples will be collected from all subjects at specified time points to evaluate concentrations of BMS-986179 and nivolumab. PK parameters such as Cmax, Ctrough, Tmax, T-HALF, AUC (TAU), CLT and accumulation index (AI) will be derived, if feasible, from serum concentration versus time data. Serum samples will be collected from subjects in to evaluate concentrations of nivolumab. Immunogenicity Measures: Serum samples to evaluate development of anti-drug antibodies (ADA) response to BMS-986179 alone, and in combination with nivolumab will be collected at specified time points. Efficacy Measures: Disease assessment with CT and/or MRI, as appropriate, will be performed at baseline and every 8 weeks until disease progression. Once disease progression is noted no more protocol required tumor assessments are needed unless treatment is continued beyond progression. In this case tumor assessments will continue every 8 weeks until confirmed disease progression or study treatment is discontinued. | — |
Countries
Netherlands
Outcome results
None listed