Single-Agent MOR208 in Relapsed or Refractory (R-R) Non-Hodgkin's Lymphoma (NHL): Results from Diffuse Large B-Cell Lymphoma (DLBCL) and Indolent NHL Subgroups of a Phase IIa Study

• Published in: Blood 2016-12, Vol.128 (22), p.623-623
• Main Authors: Jurczak, Wojciech, Zinzani, Pier Luigi, Gaidano, Gianluca, Goy, Andre, Provencio, Mariano, Nagy, Zsolt, Robak, Tadeusz, Maddocks, Kami J., Buske, Christian, Ambarkhane, Sumeet, Winderlich, Mark, Dirnberger-Hertweck, Maren, Endell, Jan, Blum, Kristie A
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.623.623

Introduction: The B-lymphocyte, lineage specific surface antigen CD19 is broadly and homogeneously expressed in most B-cell non-Hodgkin's lymphomas (NHL). As a co-stimulatory molecule of the B-cell receptor complex it is an important regulator of transmembrane signals in B-cells. Phosphorylation of intracellular tyrosine residues of CD19 may augment signal transduction in multiple pro-survival and proliferation pathways ( e.g. PI3K and BTK). This makes CD19 an attractive target for the treatment of B-cell malignancies. MOR208 is a Fc-enhanced CD19 monoclonal antibody. The Fc-enhancement of MOR208 leads to a potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). MOR208 also induces direct cytotoxicity, potentially by disrupting B-cell receptor (BCR) signalling. Thus MOR208 may have clinical use as a new therapeutic agent in patients with (R-R) B-cell malignancies. Methods: This is an open-label, multicenter, phase IIa study of MOR208 in R-R NHL patients progressing after at least one prior rituximab-containing therapy. Patients were enrolled into 1 of 4 cohorts of aggressive and indolent (i) NHLs. Treatment comprised single-agent MOR208, 12 mg/kg IV, weekly, for 8 weeks (2 cycles), which could continue for 4 additional weeks in patients with at least stable disease (SD) after 2 cycles. Patients with complete responses (CRs) or partial responses (PRs) at 12 weeks could continue with bi-weekly or monthly MOR208 treatment until progression. The primary endpoint was the objective response rate (ORR), which was assessed by the investigator. Secondary endpoints included progression-free survival (PFS), duration of response (DoR) as well as incidence and severity of adverse events (AEs). This analysis includes the evaluation of potentially predictive and prognostic biomarkers in DLBCL and iNHL cohorts. Results: In total, 92 patients were enrolled including 35 (38%) with DLBCL and 45 (49%) with iNHL. Median age was 71 years in the DLBCL cohort and 66 years in the iNHL cohort. 30 (86%) DLBCL patients and 40 (89%) iNHL patients had stage III-IV disease; 12 (34%) and 21 (47%) had received ≥3 prior lines of therapy, respectively. In the DLBCL cohort 24 (69%) patients were rituximab refractory as were 22 (49%) patients in the iNHL cohort. ORR was 26%, including 2 CRs and 7 PRs in the DLBCL cohort, and 29% including 5 CRs and 8 PRs in the iNHL cohort; 5/9 and 5/13 responders were rituximab refractory