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. 2023 Jan 31:1-10.
doi: 10.1080/07357907.2022.2162073. Online ahead of print.

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

Chenyu Lin  1 , Ahmed Galal  1 , David Rizzieri  2 , Sant Chawla  3 , Seung T Lee  4 , Angela Georgy  5 , Kristina Dabovic  5 , Thomas Strack  5 , Matthew McKinney  1
Affiliations

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

Chenyu Lin et al. Cancer Invest. .

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.

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Conflict of interest statement

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.

Figures

Fig 1.
Fig 1.
Swimmer’s plot demonstrating each patient’s response to therapy. Only patients with at least one response evaluation were included. Length of bar represents time to progression or off trial. One patient (ID 1004-005) experienced a prolonged CR despite being off all lymphoma-directed therapies. Fig 1B. Waterfall plot depicting best tumor response of target lesions by patient, based on maximal percentage of tumor reduction as assessed by the change in the sum of the products of perpendicular diameters (SPPD) on computed tomography. All but one of the evaluable patients had a greater than 50% reduction in target lesion tumor volume as best response. Fig 1C, 1D. Kaplan-Meier survival analysis demonstrating an estimated 12-month overall survival of 71.4% (95% CI, 44.7–100), and a 12-month progression free survival of 28.6% (95% CI, 8.9–92.2).
Fig 2.
Fig 2.
Serum albumin trends during cycle 1 in patients who experienced capillary leak syndrome (CLS) vs did not experience CLS. In both patients with CLS, there was a more profound drop in serum albumin in the first five days. Arrows indicate time of CLS diagnosis.
Fig 3.
Fig 3.
Mean percent change of circulating CD19-expressing B cell counts from pre-treatment values. Error bars refer to standard deviation.
See this image and copyright information in PMC

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