Data from Targeting the Inducible T-cell Costimulator (ICOS) in patients with Relapsed/Refractory T-Follicular Helper Phenotype Peripheral T-Cell and Angioimmunoblastic T-Cell Lymphoma

Abstract

<div>Abstract<p>Purpose: Proliferation of T-follicular helper (T<sub>FH</sub>) CD4+ T-cells is a postulated pathogenic mechanism for T-cell non-Hodgkin’s lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by T<sub>FH</sub>, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models. Patients and Methods: We report the safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT) and recommended phase 2 dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791). Results: Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01 mg/kg to 3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29 - 86) and the median prior lines of therapies was 3 (1 - 16). Most common grade 3 or 4 adverse events were decreased CD4+ T-cells (57%), lymphopenia (22%), anemia (13%), and infusion related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on T<sub>FH</sub> cells. The response rate in AITL was 44%. Conclusions: MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes.</p></div>