Safety and efficacy of anti-CD20 immunotoxin MT-3724 in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) in a phase I study.

Fanale, Michelle A.; Hamlin, Paul A.; Park, Sophie; Persky, Daniel O.; Higgins, Jack P.; Burnett, Christine; Dabovic, Kristina; Poma, Eric E.; Sarapa, Nenad; Younes, Anas

doi:10.1200/jco.2018.36.15_suppl.7580

Cited by 9 publications

(5 citation statements)

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“…MT-3724 is an engineered toxin antibody (ETB) that comprises of a single-chain variable fragment of an antibody targeting CD-20 and a Shiga like toxin subunit A inactivating the ribosomal activity. In a first in human study with MT-3724, 24 patients with r/r NHL have been treated including 21 patients in 6 dose escalation doses (range from 5–100 μg/kg/dose) and three patients in the MTD cohort at 75 μg/kg/dose [40]. Peripheral edema, fatigue, diarrhea, myalgia, and cough were the most common AEs reported.…”

Section: Immunotherapymentioning

confidence: 99%

Novel and emerging therapies for B cell lymphoma

Ayyappan

Maddocks

2019

J Hematol Oncol

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Lymphomas are a heterogeneous group of lymphoproliferative disorders, with unique clinical and biological characteristics that exhibit variable response to therapy. Advances in chemo-immunotherapy have improved outcomes in a number of lymphoma subtypes; however, the prognosis for many patients with relapsed and refractory disease remains poor. Novel therapies including several small molecule inhibitors and chimeric antigen receptor T cells have been approved for the treatment of different lymphoma subtypes at relapse, changing the therapy landscape and further improving survival in many of these diseases. This has led to a focus on the development of new cellular therapy, antibody-based therapy, and small molecule inhibitors for relapsed and refractory disease that offer an alternative approach to cytotoxic chemotherapy. We will review these promising novel therapies and discuss their safety and efficacy in first in human studies.

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Section: Immunotherapymentioning

confidence: 99%

Novel and emerging therapies for B cell lymphoma

Ayyappan

Maddocks

2019

J Hematol Oncol

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“…MT-3724 is a novel ADC directed against CD20, which is comprised of a single-chain variable fragment lined to Shiga-like toxin-1A, a ribosome-inactivating protein. Phase I trial of MT-3724 monotherapy in heavily pretreated DLBCL patients reported an ORR of 30% [ 57 ], with the phase II trial already being underway [ 58 ]. Radiolabeled CD20 mAbs currently used in clinical testing include ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar), chelated with yttrium-90 and iodine-131, respectively.…”

Section: Monoclonal Antibodies and Antibody–drug Conjugatesmentioning

confidence: 99%

New agents and regimens for diffuse large B cell lymphoma

2020

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As a widely recognized standard regimen, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is able to cure two-thirds patients with diffuse large B cell lymphoma (DLBCL), and the remaining patients suffer from refractory or relapsed disease due to resistance to R-CHOP and fare poorly. Unsatisfied outcomes for those relapsed/refractory patients prompted efforts to discover new treatment approaches for DLBCL, including chimeric antigen receptor T cells, bispecific T cell engagers, immunomodulatory drugs, immune checkpoint inhibitors, monoclonal antibodies, antibody–drug conjugates, molecular pathway inhibitors, and epigenetic-modifying drugs. Herein, up-to-date data about the most promising treatment approaches for DLBCL are recapitulated, and novel genetic classification systems are introduced to guide individualized treatment for DLBCL.

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“…MT-3724 is an innovative engineered anti-CD20 ADC that contains a variable fragment (scFv) bonded to Shiga-like toxin-1A (SLTA), which expedites both internalization and cell killing by ribosomal inhibition. The results of a phase I trial (NCT02361346) of MT-3724 monotherapy demonstrated clinical anti-neoplastic activity in heavily pretreated R/R B-NHL patients, especially in the advanced-stage DLBCL subset with an ORR of 30% [ 100 ]. The most common AEs related to the drug were edema (67%), fatigue (43%), diarrhea (38%), myalgia (38%), and cough (33%).…”

Section: Adcs Explored In Various Clinical and Preclinical Settingsmentioning

confidence: 99%

Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress

2021

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Antibody-drug conjugates (ADCs) are a promising class of immunotherapies with the potential to specifically target tumor cells and ameliorate the therapeutic index of cytotoxic drugs. ADCs comprise monoclonal antibodies, cytotoxic payloads with inherent antitumor activity, and specialized linkers connecting the two. In recent years, three ADCs, brentuximab vedotin, polatuzumab vedotin, and loncastuximab tesirine, have been approved and are already establishing their place in lymphoma treatment. As the efficacy and safety of ADCs have moved in synchrony with advances in their design, a plethora of novel ADCs have garnered growing interest as treatments. In this review, we provide an overview of the essential elements of ADC strategies in lymphoma and elucidate the up-to-date progress, current challenges, and novel targets of ADCs in this rapidly evolving field.

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Safety and efficacy of anti-CD20 immunotoxin MT-3724 in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) in a phase I study.

Cited by 9 publications

References 0 publications

Novel and emerging therapies for B cell lymphoma

Novel and emerging therapies for B cell lymphoma

New agents and regimens for diffuse large B cell lymphoma

Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress

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