Benner, Brooke;
Duggan, Megan;
Stiff, Andrew;
Konda, Bhavana;
Rupert, Robert D.;
Monk, Paul;
Verschraegen, Claire;
Shah, Hiral;
Noonan, Anne;
Carson, William E.;
Wesolowski, Robert
Abstract CT169: Pilot study testing the effects of BTK inhibitor ibrutinib and nivolumab on levels and function of myeloid-derived suppressor cells and other immune subsets in patients with metastatic solid tumors (NCT03525925)
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Medientyp:
E-Artikel
Titel:
Abstract CT169: Pilot study testing the effects of BTK inhibitor ibrutinib and nivolumab on levels and function of myeloid-derived suppressor cells and other immune subsets in patients with metastatic solid tumors (NCT03525925)
Beteiligte:
Benner, Brooke;
Duggan, Megan;
Stiff, Andrew;
Konda, Bhavana;
Rupert, Robert D.;
Monk, Paul;
Verschraegen, Claire;
Shah, Hiral;
Noonan, Anne;
Carson, William E.;
Wesolowski, Robert
Erschienen:
American Association for Cancer Research (AACR), 2019
Erschienen in:
Cancer Research, 79 (2019) 13_Supplement, Seite CT169-CT169
Beschreibung:
Abstract Background: Myeloid-derived suppressor cells (MDSC) are a naturally occurring population of immature myeloid cells with immune suppressive function that curtail inflammatory processes. In cancer, these cells abnormally expand and migrate to tumor/lymphoid regions where they negatively impact antigen specific and innate immune effector cells. Circulating MDSC levels have also been associated with the higher tumor burden and decreased survival of patients with solid tumors. Preclinical studies performed by our group demonstrated that ibrutinib (PCI-32765), an irreversible inhibitor of Bruton’s tyrosine kinase, is capable of inhibiting MDSC generation and their immunosuppressive function (A. Stiff, CA Res, 2016). We also found that the combination of ibrutinib and a PD-L1 inhibitor worked synergistically in a mouse model of mammary carcinoma. Based on these results, targeting MDSC with ibrutinib has the potential to enhance the efficacy of immune checkpoint inhibitors such as nivolumab in patients with advanced solid tumors. Materials and Methods: This pilot study will assess the effect of single agent ibrutinib and ibrutinib in combination with nivolumab on levels and function of circulating myeloid-derived suppressor cells in 15 patients with advanced solid tumors. Eligible patients are required to have metastatic malignancy and be eligible for treatment with nivolumab as determined by the treating physician. Study subjects will be treated with ibrutinib at 420 mg given orally once daily. Nivolumab will be given at a standard dose of 240 mg IV over 30 minutes on days 1 and 15 on 28-day cycles. Ibrutinib dosing will be started 7 (+/-2) days prior to cycle 1 of nivolumab therapy and will be given until cycle 1, day 8 of nivolumab or total of 15 days (whichever comes first). Peripheral blood will be collected just prior to initiation of ibrutinib (at day -7), prior to day 1 of cycle 1, prior to day 8 of cycle 1, prior to day 1 of cycle 2 and at the time of disease progression. The primary objective is to evaluate the effect of the ibrutinib therapy on circulating levels of myeloid-derived suppressor cells (MDSC). The safety of the study combination, effect of ibrutinib/nivolumab on immune cell subsets and the length of progression-free survival will also be assessed. Conclusion: The study opened to accrual on August 10, 2018 and is currently enrolling the target 15 patients. To date 9 patients are on study. Citation Format: Brooke Benner, Megan Duggan, Andrew Stiff, Bhavana Konda, Robert D. Rupert, Paul Monk, Claire Verschraegen, Hiral Shah, Anne Noonan, William E. Carson, Robert Wesolowski. Pilot study testing the effects of BTK inhibitor ibrutinib and nivolumab on levels and function of myeloid-derived suppressor cells and other immune subsets in patients with metastatic solid tumors (NCT03525925) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT169.