Combinatorial Efficacy and Toxicity of an Engineered Toxin Body MT-3724 with Gemcitabine and Oxaliplatin in Relapsed or Refractory Diffuse Large B Cell Lymphoma

Abstract

MT-3724 is an engineered direct-kill immunotoxin comprised of a CD20-specific scFv fused to a Shiga-like toxin subunit. In this phase IIa study, eight patients with relapsed diffuse large B-cell lymphoma were treated with MT-3724 combined with gemcitabine and oxaliplatin (GEMOX). The objective response rate was 85.7%, with a median duration of response of 2.2 months. The 12-month overall survival and progression-free survival were 71.4% and 28.6%, respectively. Two patients experienced grade 2 capillary leak syndrome (CLS). Combination therapy with MT-3724 and GEMOX demonstrated an early efficacy signal but was limited by the incidence of CLS.

Keywords:

• Clinical trials
• immunology/immunobiology
• lymphomas
• therapy

Declaration of interest

Authors CL and SL have no declarations of interest to report. Author AGa reports speaker’s bureau from Kite, Incyte, and SeaGen; Ad boards with Kite and SeaGen; research funding from Iovance and CRISPR. Author DR reports honoraria and/or speakers’ bureau from Gilead/Kite, Seattle Genetics, Stemline, Incyte, Karyopharm, Jazz, Pfizer, Amgen, and Pharmacyclics; advisory committee membership on AbbVie, AROG, Bayer, Sanofi, Teva, Acrotech, Seattle Genetics, Stemline, Incyte, Karyopharm, Celgene, Celltrion, Mustang, Novartis, Jazz, Pfizer. Author SC reports funding/contracts from Amgen, Roche, GlaxoSmithKline, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research though Collaboration, Janssen, Advenchen Laboratories, Bayer, InhibRx, NKMax, TYME Inc., AADI Bioscience, Cellestia Biotech, Immix BioPharma; consulting from Amgen, Roche, GlaxoSmithKline, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research though Collaboration, Janssen, Advenchen Laboratories, Bayer, NKMax, InhibRx, AADI Bioscience, Cellestia Biotech, Immix BioPharma; and ownership of stock or stock options in AADi, Cellestia Biotech, Immix BioPharma. Authors AGe, KD, and TS are employees of Molecular Templates. Author MK reports honoraria and speakers’ bureau from Gilead/Kite; consulting or advisory from Kite/Gilead, Seattle Genetics, Molecular Templates, BTG, Pharmacyclics, Verastem, Genentech, Celgene; and research funding from UNUM, Molecular Templates, Incyte, Beigene, Denovo Biopharma, Pharmacyclics, Nordic Nanovector, BMS, Genentech, Celgene.

Additional information

Funding

This clinical trial and author MM were supported by research funding from Molecular Templates and the Duke Cancer Institute. Author CL was supported by the Duke Hematology & Transfusion Medicine T32 training grant (NIH/NHLBI HL007057-46).