Solid tumors MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Written IC 2. Population a) Subjects must be > 18 years old/have histologic or cytologic confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease and have at least 1 lesion that is biopsy-accessible. b) Part 1A/Part 1B: i) Subjects must have received, and then progressed/been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting, if such a therapy exists and have been considered for all other potentially efficacious therapies prior to enrollment. Subjects who are ineligible for standard therapy (due to medical factors) will be allowed to enroll provided their refusal/ineligibility is documented in records. ii) 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. c) Part 2: i) For ovarian cancer (1) Subjects must have received and progressed/been intolerant of at least 1 prior platinum-containing treatment regimen and have been considered for all other potentially efficacious therapies. (2) Subjects who are sensitive to platinum must have received at least 2 prior platinum-containing lines of treatment. ii) For CRC: (1) Subjects must have received and progressed/been intolerant of at least 1 standard systemic therapy for metastatic and/or unresectable disease (or have progressed within 6 months of adjuvant therapy) and have been considered for all other potentially efficacious therapies. (2) Subjects must have known KRAS mutation status. iii) For gastric cancer: (1) Subjects must have received and progressed/been intolerant of at least 1 prior standard systemic therapy for metastatic and/or unresectable disease (or have progressed within 6 months of adjuvant therapy) and have been considered for all other potentially efficacious therapies. (a) Subjects must have known HER2 mutation status. Subjects with tumors overexpressing HER2 must have received prior HER2 therapy or have a medical reason for ineligibility. iv) For pancreatic cancer: (1) Subjects must have received and progressed/been intolerant of (or not be a candidate for) at least 1 prior standard therapy and have been considered for all other potentially efficacious therapies. d) Subjects must have an Eastern Cooperative Oncology Group performance status of = 1. e) Subjects must have at least one lesion with measureable disease f) Subjects who have had prior exposure to therapy with any agent specifically targeting checkpoint pathway inhibition are permitted after a washout period of any time > 4 weeks from the last treatment. g) Subjects with prior therapy with any agent specifically targeting T-cell co-stimulation pathways such as anti-glucocorticoid induced tumor necrosis factor receptor, anti-CD137, or anti-OX40 antibody, with exceptions, are permitted after a washout period of any time > 4 weeks from the last treatment. h) Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose of the study drug. i) Subject must consent to a pre-treatment tumor biopsy. Subjects must also consent to the acquisition of existing formalin-fixed paraffin-embedded tumor tissue (if available), either a block or 15 to 20 unstained slides, for performance of correlative studies. j) Pre-treatment biopsy tissue may have been collected at any time during the screening period prior to the first dose of the study drug. k) Subjects must have adequate organ
Exclusion criteria
Exclusion criteria: 1. Target Disease Exceptions a) Subjects with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded. However, subjects with controlled brain metastases will be allowed to enroll. b) Subjects with carcinomatous meningitis are excluded. c) 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. d) For pancreatic cancer: Subjects with clinically relevant ascites at baseline (defined as requiring paracentesis) or with moderate radiographic ascites are excluded. 2. Medical History and Concurrent Diseases a) Subjects with a prior malignancy, different from the one used for enrollment in this study, diagnosed less than 2 years ago are excluded. Subjects with second malignancies diagnosed more than 2 years ago who have received therapy with curative intent with no evidence of disease during the interval and who are considered by the investigator to present a low risk for recurrence will be eligible. b) Subjects with other active malignancy requiring concurrent intervention are excluded. c) Subjects with prior organ allograft are excluded. d) Subjects who have received prior anti-cancer treatments are permitted e) Subjects who have received prior therapy with an anti-CD73 antibody, an anti-CD39 antibody, or an adenosine 2A receptor inhibitor are excluded. f) Subjects with a prior history of deep vein thrombosis within the last 6 months, or arterial thrombus at any time are excluded. g) Subjects with active, known or suspected autoimmune disease, with a few exceptions. h) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity are excluded. i) Subjects with chronic obstructive pulmonary disease requiring recurrent steroids bursts or chronic steroids at doses greater than 10 mg/day of prednisone or the equivalent are excluded. j) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease are excluded. Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study drug is permitted. k) Subjects with uncontrolled or significant cardiovascular disease are excluded. l) Subjects with active hepatitis as evidenced by the following are excluded: i) Positive test for hepatitis B surface antigen ii) Positive test for hepatitis C antibody and/or qualitative viral load m) Subjects with evidence of active bacterial, viral, or fungal infections less or equal to 7 days prior to initiation of study drug therapy are excluded. n) Subjects with a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded. o) Subjects with evidence or history of active or latent tuberculosis infection are excluded. p) Subjects who have undergone any major surgery within 4 weeks of study drug administration are excluded. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of the st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the safety and tolerability of BMS-986179 administered alone and/or in combination with nivolumab.;Secondary Objective: -) To characterize the PD activity of BMS-986179 administered alone and in combination with nivolumab -) To assess the preliminary anti-tumor activity of BMS-986179 in combination with nivolumab as measured by objective response rate (ORR), DOR, and progression-free survival rate (PFSR) -) To characterize the PK and immunogenicity of BMS-986179 administered alone and in combination with nivolumab -) To characterize the immunogenicity of nivolumab when administered in combination with BMS-986179;Primary end point(s): The primary objective of the study is to assess the safety and tolerability of BMS-986179 administered alone and/or in combination with nivolumab. The assessment of safety will be based on the incidence of AEs, SAEs, AEs leading to discontinuation, and deaths. In addition, clinical laboratory test abnormalities will be examined.;Timepoint(s) of evaluation of this end point: see above section | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The first secondary objective (PD effect of CD73 inhibition) will be measured by CD73 enzyme assays and CD73 IHC in pre- and on-treatment tumor biopsies. The anti-tumor activity of BMS-986179 in combination with nivolumab will be measured by ORR, DOR, and PFSR at 24 weeks and will be based on RECIST 1.1 for solid tumors. Disease assessment with CT and/or MRI as appropriate will be performed at baseline, every 8 weeks from the start of combination treatment for the Q1W and Q2W regimens, or every 9 weeks from the start of combination treatment for the Q3W regimen until treatment discontinuation or completion, and then every 12 weeks for the first year until further disease progression, start of a new treatment, lost to follow-up, or death, whichever comes first. The PK will be characterized by assessment of PK parameters of BMS-986179, and immunogenicity will be assessed by the frequency of positive ADA to BMS-986179 and nivolumab.;Timepoint(s) of evaluation of this end point: see above section. | — |
Countries
Australia, Canada, France, Germany, Israel, Italy, Netherlands, United States
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed