Phase I study of a bispecific ligand-directed toxin targeting CD22 and CD19 (DT2219) for refractory B-cell malignancies

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Veronika BachanovaDaniel A Vallera

Abstract

The novel bispecific ligand-directed toxin (BLT) DT2219 consists of a recombinant fusion between the catalytic and translocation enhancing domain of diphtheria toxin (DT) and bispecific single-chain variable fragments (scFV) of antibodies targeting human CD19 and CD22. We conducted a phase I dose-escalation study to assess the safety, maximum tolerated dose, and preliminary efficacy of DT2219 in patients with relapsed/refractory B-cell lymphoma or leukemia. DT2219 was administered intravenously over 2 hours every other day for 4 total doses. Dose was escalated from 0.5 μg/kg/day to 80 μg/kg/day in nine dose cohorts until a dose-limiting toxicity (DLT) was observed. Twenty-five patients with mature or precursor B-cell lymphoid malignancies expressing CD19 and/or CD22 enrolled to the study. Patients received median 3 prior lines of chemotherapy and 8 failed hematopoietic transplantation. All patients received a single course of DT2219; one patient was retreated. The most common adverse events, including weight gain, low albumin, transaminitis, and fever were transient grade 1-2 and occurred in patients in higher dose cohorts (≥40 μg/kg/day). Two subjects experienced DLT at dose levels 40 and 60 μg/kg. Durable objective responses ...Continue Reading

References

Aug 1, 1995·Leukemia & Lymphoma·R H Scheuermann, E Racila
Dec 4, 1998·Biochemistry·A Keppler-HafkemeyerI Pastan
Mar 11, 2003·Nature Biotechnology·Joan E SmallshawEllen S Vitetta
Apr 30, 2003·Seminars in Oncology·Alessandra Cesano, Urte Gayko
May 18, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel A ValleraHua Chen
Jul 16, 2008·Radiologic Clinics of North America·Bruce D Cheson
Mar 3, 2011·Statistics in Medicine·Ying Yuan, Guosheng Yin
Oct 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert J Kreitman, Ira Pastan
Feb 23, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert J KreitmanIra Pastan
Mar 1, 2014·Blood·Alan S WayneIra Pastan

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Citations

Oct 6, 2015·Trends in Pharmacological Sciences·Takashi AngataMatthew S Macauley
Jun 5, 2016·Current Opinion in Organ Transplantation·Akimichi Inaba, Menna R Clatworthy
Oct 21, 2016·Computational and Structural Biotechnology Journal·Marco Ruella, Marcela V Maus
Dec 31, 2016·International Journal of Molecular Sciences·Fa YangWeijun Qin
Jun 14, 2017·Expert Opinion on Pharmacotherapy·Raoul SantiagoHenrique Bittencourt
Sep 30, 2020·Journal of Cancer Research and Clinical Oncology·Shuyu HuangAndrea van Elsas
Dec 19, 2018·Frontiers in Immunology·Sarah J MeyerLars Nitschke
Nov 5, 2019·Frontiers in Microbiology·Fatemeh ShafieeAli Jahanian-Najafabadi
Mar 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xui-Fen LiuIra Pastan
May 28, 2020·Frontiers in Immunology·Margaux LejeuneJo Caers
Dec 24, 2018·Biomedicines·Daniel A Vallera, Robert J Kreitman
Oct 7, 2020·Journal for Immunotherapy of Cancer·Natalia Rodrigues MantuanoHeinz Läubli
Jan 6, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lotfi Abou-ElkacemJürgen K Willmann
Nov 4, 2016·Molecular Cancer Therapeutics·Bart E C G de GoeijPaul W H I Parren
Feb 15, 2017·Molecular Cancer Therapeutics·Antonella BorgattiDaniel A Vallera
Nov 2, 2019·Journal of Pharmaceutical Sciences·Ji-Sun KimYong-Sung Kim
Jan 23, 2021·Bioorganic & Medicinal Chemistry·Aiko YamaguchiKyoji Tsuchikama
Feb 23, 2021·Journal of Drug Targeting·Mohammad Reza KhirehgeshBahman Akbari
Jun 3, 2021·International Journal of Molecular Sciences·Elena GianchecchiAlessandra Fierabracci

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