Enowmpey Enowtambong

Supplemental Figure 2. MEDI-570 effects on lymphocyte and leukocyte populations. Baseline-normalized, absolute counts (ABS) of circulating cell populations were plotted on study days 1, 7, 14 and 21 from patients enrolled in each dose group as indicated. A) Total CD3+CD8+ cytotoxic T cells B) CD14+ monocytes C) CD3-CD56+ and/or CD16+ NK cells D) CD3-CD19+ B cells.

Supplemental Figure 1. CD4 count recovery after end of treatment (by local site collection)

Supplemental Tables and Protocol Description

Supplemental Figure 3. Representative baseline pre-treatment tumor specimen of a patient with AITL (H&E, ICOS staining and CD3 staining by IHC)

Purpose:Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, 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 II 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 (0.01–3 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 TFH 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.

Supplemental Figure 2. MEDI-570 effects on lymphocyte and leukocyte populations. Baseline-normalized, absolute counts (ABS) of circulating cell populations were plotted on study days 1, 7, 14 and 21 from patients enrolled in each dose group as indicated. A)Total CD3+CD8+ cytotoxic T cells B) CD14+ monocytes C) CD3-CD56+ and/or CD16+ NK cells D) CD3-CD19+ B cells.

Supplemental Tables and Protocol Description

Supplemental Figure 3. Representative baseline pre-treatment tumor specimen of a patient with AITL (H&E, ICOS staining and CD3 staining by IHC)