B-MIND: MOR208 plus bendamustine (BEN) versus rituximab (RTX) plus BEN in patients with relapsed or refractory (R-R) diffuse large B-cell lymphoma (DLBCL): An open-label, randomized phase II/III trial.

TPS7571 Background: Patients ineligible for stem cell transplantation (SCT) or who relapse after SCT, and those who fail to respond to second-line or salvage chemotherapy, represent an unmet medical need for which new therapeutic strategies are required. MOR208 is a novel Fc-enhanced, humanized, monoclonal antibody directed against CD19. Significant single-agent activity of MOR208 in patients with R-R DLBCL (Jurczak et al., J Clin Oncol 34, 2016 [suppl; abstr 7545]) and enhancement of MOR208-mediated cytotoxicity by BEN in preclinical studies, provide a strong rationale to study MOR208 + BEN in patients with R-R DLBCL. Methods: B-MIND is a randomized (1:1), two-arm, multicenter, open-label, adaptive design, phase II/III study of MOR208 + BEN vs RTX + BEN in adult patients with histologically confirmed DLBCL who have relapsed after or are refractory to 1 to 3 prior lines of therapy and who are not candidates for high-dose chemotherapy and autologous SCT. At least 1 prior therapy line must have included a CD20-targeted therapy. Other key inclusion criteria: age ≥18 years; measurable disease; availability of tumor tissue for central pathology review; ECOG 0–2, and adequate major organ systems function. Key exclusion criteria: primary refractory DLBCL; central nervous system involvement, and known double/triple hit DLBCL genetics. The safety of the combination will be assessed in an initial phase II evaluation. Treatment will comprise 6 cycles of MOR208 (12 mg/kg IV) + BEN (90 mg/m 2 IV) or RTX 375 mg/m 2 IV + BEN. Patients achieving a response after cycle 6 will continue to receive antibody treatment for up to 18 additional cycles. Primary endpoint: progression-free survival (PFS); secondary endpoints include: best overall response, overall survival, safety, quality of life, immunogenicity and pharmacokinetics. Enrollment of 330 patients is anticipated in Europe, US and Asia-Pacific countries. Fourteen patients have been randomized to date. Clinical trial information: NCT02763319.