Publication Date:
2020-11-05
Description:
Background: Engineered toxin bodies (ETBs) are comprised of a proprietarily engineered form of Shiga-like toxin A subunit (SLT-A) genetically fused to antibody-like binding domains. ETBs work through novel mechanisms of action and are capable of forcing internalization, self-routing through intracellular compartments to the cytosol, and inducing potent cell-kill via the enzymatic and permanent inactivation by SLT-A of ribosomes. MT-3724 represents a novel ETB modality comprised of an anti-CD20 single-chain variable fragment genetically fused to SLT-A, is capable of efficient internalization once bound to CD20 and can induce potent direct cell-kill via enzymatic ribosome inactivation. In a Phase 1/1b dose escalation/expansion study of MT-3724 monotherapy in subjects with heavily pretreated (including CD20 monoclonal antibodies) relapsed or refractory B-cell non-Hodgkin lymphoma (r/rNHL) the most common grade ≥3 treatment-related adverse events were myalgia and neutropenia (n=3 each). Dose-limiting toxicities (DLTs) were indicative of innate immune response. In subjects with negative rituximab serum concentrations there was a 38% objective response rate (Hamlin et al. ASH 2019). MT-3724 is currently being studied in five ongoing (three actively recruiting, two in development) Phase 2 studies for r/rNHL. This study will evaluate the safety, tolerability, recommended phase 2 dose (RP2D), efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of MT-3724 in two cohorts of subjects with r/r mantle cell lymphoma (r/rMCL). Study Design and Methods: This phase 1, multicenter, open-label, single arm study will include adults ≥18 yrs with histologically confirmed r/rMCL (histology plus expression of Cyclin D1 in association with CD20 and CD5 or evidence of t(11:14)) who have received ≥2 prior systemic therapies (including anti-CD20 antibody alone or in combination with other agents) and have ≥1 measurable lesion (Lugano criteria). Subjects with CNS involvement or recent treatment with rituximab (within 84 days of study initiation; if received within 12-37 weeks of start of treatment, serum rituximab level must be confirmed to be negative [
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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