Phase 1/2 trial of anti-CD7 allogeneic WU-CART-007 for patients with relapsed/refractory T-cell malignancies
Abstract
Abstract Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL; T-ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T-cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3+3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received 1 infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 28 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 × 106 cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Two grade 1 immune effector cell–associated neurotoxicity syndrome events (7.7%) and 1 grade 2 acute graft-versus-host disease event occurred (3.8%). One grade 2 immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome was observed. Among the 11 patients evaluable for response at the RP2D who received enhanced lymphodepleting chemotherapy, the overall response rate was 90.9%, and the composite complete remission rate was 72.7%. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. This trial was registered at www.ClinicalTrials.gov as #NCT04984356.
Article Details
Authors (33)
Armin Ghobadi
5Washington University School of Medicine, St. Louis, United States
Ibrahim Aldoss
Shannon L. Maude
Deepa Bhojwani
Alan S. Wayne
4Children’s Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA
Ashish Bajel
5Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, University of Melbourne, Department of Clinical Haematology, Melbourne, Australia
Bhagirathbhai Dholaria
Rawan Faramand
24Moffitt Cancer Center and Research Institute, Tampa, FL
Ryan J. Mattison
8University of Wisconsin Carbone Cancer Center, Madison, WI
Anita Rijneveld
13Erasmus University Medical Center, Department of Hematology, Rotterdam, Netherlands
C. Michel Zwaan
1Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Friso Calkoen
1Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
Andre Baruchel
Nicolas Boissel
Michael Rettig
5Washington University School of Medicine, St. Louis, United States
Brent Wood
11University of Washington, Seattle, United States
Kenneth Jacobs
14Mersana Therapeutics, Boston, MA
Stephanie Christ
1Washington University School of Medicine, Division of Oncology, St. Louis, United States
Haley Irons
15Wugen, St. Louis, MO
Ben Capoccia
15Wugen, St. Louis, MO
Deborah Masters
15Wugen, St. Louis, MO
Justo Gonzalez
15Wugen, St. Louis, MO
Tony Wu
Department of Neurology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital
Maria del Rosario
5Bioheng Biotech Co., Ltd., Nanjing, China
Alexander Hamil
1Wugen, Inc, St. Louis, United States
Ouiam Bakkacha
15Wugen, St. Louis, MO
John Muth
15Wugen, St. Louis, MO
Brett Ramsey
15Wugen, St. Louis, MO
Eileen McNulty
5Bioheng Biotech Co., Ltd., Nanjing, China
Jan Baughman
16Alviso Clinical Research, San Francisco, CA
Matthew L. Cooper
15Wugen, St. Louis, MO
Jan Davidson-Moncada
5Bioheng Biotech Co., Ltd., Nanjing, China
John F. DiPersio
Department of Medicine, Washington University School of Medicine, St. Louis