Metastatic Malignant Solid Neoplasm Clinical Trial
Official title:
Phase I/Ib Trial Evaluating the Safety and Efficacy of BET Inhibitor, ZEN003694 With PD-1 Inhibitor, Nivolumab With or Without CTLA-4 Inhibitor, Ipilimumab in Solid Tumors
This phase I/Ib trial is to find out the best dose, possible benefits and/or side effects of BET bromodomain inhibitor ZEN-3694 (ZEN003694) when given in combination with nivolumab with or without ipilimumab in treating patients with solid tumors. ZEN003694 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ZEN003694 in combination with nivolumab with or without ipilimumab may shrink or stabilize solid tumors.
PRIMARY OBJECTIVE: I. To evaluate the safety/tolerability and recommended phase 2 dose (RP2D) of the BET inhibitor (BETi) ZEN003694 when combined with nivolumab with or without low dose ipilimumab in solid tumors. SECONDARY OBJECTIVES: I. To evaluate the efficacy of the triplet regimen in a cohort of patients with recurrent platinum-resistant BRCA wild type (wt) epithelial ovarian cancer. Ia. To observe and record anti-tumor activity. II. To evaluate the impact of BET inhibition on the tumor immune microenvironment (TIME). III. To explore predictors of response and resistance to therapy. IV. To characterize the pharmacokinetic (PK) profile of ZEN003694 and its active metabolite ZEN003791. EXPLORATORY OBJECTIVE: I. To correlate drug exposure with response and/or toxicity. OUTLINE: This is a dose-escalation study of ZEN003694 followed by a dose-expansion study. DOSE ESCALATION (DOUBLET TREATMENT): Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and ZEN003694 orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI), a computed tomography (CT) scan, a positron emission tomography (PET) scan, and/or an x-ray as well as blood sample collection throughout the trial. Patients also undergo a biopsy during screening. DOES ESCALATION AND DOSE EXPANSION (TRIPLET TREATMENT): Patients receive nivolumab IV over 30 minutes on day 1, ipilimumab IV over 90 minutes on day 1, and ZEN003694 PO QD on days 1-21 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 5, patients are no longer treated with ipilimumab, but receive nivolumab IV over 30 minutes on day 1 and ZEN003694 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI, a CT scan, a PET scan, and/or an x-ray as well as blood sample collection throughout the trial. Patients also undergo a biopsy during screening and on study. After completion of study treatment, patients are followed up for 30 days, then every 3 months for 1 year. ;
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