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Overcoming Checkpoint Inhibitor Resistance with Epigenetic Therapy in Urothelial Cancer (GU-114)
Protocol Number:
Phase II
Noah Hahn
Johns Hopkins Kimmel Cancer Center in Baltimore
Despite the excitement over the efficacy and acceptable toxicity of immunotherapy, the majority of treated patients show primary resistance to the drug and, critically, most responders eventually lose their response through unclear mechanisms. The purpose of this study is to determine whether epigenetic reprogramming of T-lymphocytes(using guacitabine) can sensitize tumor cells to and/or reverse resistance to immune checkpoint inhibitors (immunotherapy)
INCLUSION CRITERIA - Patients must be age greater than _ 18 years; Must have histologically confirmed urothelial cancer that is advanced or metastatic; Patient must agree to provide fresh biopsy specimens and peripheral blood samples at the time of screening and during the study; Must have received or be ineligible for platinum based chemotherapy and must have received at least one line of therapy with a PD-L1 or PD-1 targeting agent; Must have normal organ and marrow functionEXCLUSION CRITERIA - Patients with active or untreated CNS disease; Patients with active auto-immune disease requiring immunosuppressive medication; Patients with active malignancies in addition to urothelial carcinoma; Patients with prior treatment with hypomethylating agents; Prior allogeneic stem cell or solid organ transplant; History of leptomeningeal disease; Uncontrolled effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); Active or prior documented inflammatory bowel disease (e.g. Crohn’s disease, ulcerative colitis); History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterations), drug-induced pneumonitis or idiopathic pneumonitis or evidence of interstitial lung disease or active non-infectious pneumonitis
Atezolizumab will be given as an IV infusion over 30 or 60 minutes on day 1 and day 22 every 6 weeks (42 days). Atezolizumab will be administered for a total of 8 cycles (16 infusions)Guadecitabine will be given as an injection in the subcutaneous tissue once daily on days 1 through 5 every 6 weeks (42 days). Guadecitabine will be administered for a total of 4 cycles.
Last Update
03/05/2019 05:03 AM