Abstract 2060: Combination of CD20 targeted engineered toxin body, MT-3724, with chemotherapy or IMiDs for the treatment of non Hodgkin's lymphoma

Autor: Caleigh Howard, Erin Willert, Jack P. Higgins, Aimee Iberg
Rok vydání: 2019
Předmět:
Zdroj: Cancer Research. 79:2060-2060
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2019-2060
Popis: MT-3724 is a novel recombinant fusion protein consisting of a CD20 binding variable fragment (scFv) fused to Shiga-like toxin-I A1 (SLTA) ribosome inactivating protein. Engineered Toxin Bodies (ETBs) are unique as they can induce internalization after binding to non- or poorly-internalizing receptors with subsequent enzymatic and permanent ribosome destruction through SLTA, representing a novel mechanism of direct cell-kill in oncology. MT-3724 has demonstrated single agent anti-tumor activity in heavily pre-treated relapsed/refractory (R/R) Non-Hodgkin’s lymphoma NHL patients in a Phase I clinical study. Specifically, in R/R diffuse large B cell lymphoma (DLBCL) patients who had low pre-existing serum levels of rituximab, an objective response rate (ORR) of 30% (3 of 10) and disease control rate of 70% (7 of 10) has been observed thus far (NCT02361346). Given the unique ribosomal inhibition mechanism of action for MT-3724, we hypothesized that combination of MT-3724 with agents possessing a differentiated mechanism of action could result in additive or synergistic cellular cytotoxicity in CD20 positive NHL cell lines. Preclinical studies were conducted to assess MT-3724 in combination with cytotoxic chemotherapeutic agents (doxorubicin, gemcitabine, bendamustine, and vincristine) or an immunomodulatory (IMiD) agent (lenalidomide) on selected NHL cell lines. The combination of MT-3724 with all agents demonstrated additive or synergistic cytotoxicity of NHL cell lines. The single agent clinical activity of MT-3724 in heavily pre-treated R/R NHL patients along with this preclinical combinatorial effect of MT-3724 with chemotherapy and IMiDs used in the treatment of R/R NHL have lead the opening of a Phase 2a study of MT-3724 in combination with Gemcitabine and oxaliplatin (GEMOX, NCT03488251) and another planned Phase 2a study of MT-3724 in combination with lenalidomide (NCT03645395). MT-3724 has demonstrated good tolerability and early signs of clinical activity as monotherapy in patients with R/R NHL along with additive and/or synergistic effects in combination with chemotherapy and IMiDs preclinically. Additional clinical studies to evaluate MT-3724 as single agent and in combination with GEMOX or lenalidomide are underway. Citation Format: Jack P. Higgins, Aimee Iberg, Caleigh Howard, Erin Willert. Combination of CD20 targeted engineered toxin body, MT-3724, with chemotherapy or IMiDs for the treatment of non Hodgkin's lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2060.
Databáze: OpenAIRE
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