Abstract
Phase 2 open label, multicenter study evaluating CRG-022, a CD22-directed autologous CAR T-cell therapy, in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) after CD19-directed CAR T-cell therapy
Journal of clinical oncology, Vol.42(16_suppl), pp.TPS7085-TPS7085
06/01/2024
DOI: 10.1200/JCO.2024.42.16_suppl.TPS7085
Abstract
TPS7085 Background: Autologous (auto) CD19-directed CAR T-cell therapy can induce long-term remissions for pts with R/R LBCL but approximately 60% will experience disease progression resulting in poor outcomes (Neelapu, 2023; Zurko, 2023). CRG-022 is a novel CAR T-cell product targeting CD22, a common B-cell antigen widely expressed in LBCL. Key features of CRG-022 include a fully human scFv derived from the m971 monoclonal antibody and 4-1BB/CD3z intracellular signaling domains (Singh, 2021). This CD22 CAR construct was developed at the National Cancer Institute and was investigated in phase (ph) 1 studies of pediatric/young adult pts with R/R CD22+ malignancies (Shah, 2020; NCT02315612) and at Stanford University in adults with R/R LBCL (Baird, 2021; NCT04088890) primarily in pts who received prior CD19-directed CAR-T therapy. The Stanford ph 1b study reported an overall response rate (ORR) and complete response rates of 66% and 52%, respectively in 29 pts treated at the recommended Phase 2 dose (RP2D) of 1x10 6 CAR+ T cells/kg (Frank, 2023). After a median follow-up of 27.3 months, the median overall survival had not been reached at the RP2D (Su, 2023). At the RP2D, no grade >3 cytokine release syndrome (CRS), immune-effector cell associated neurotoxicity syndrome (ICANS), or immune effector cell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) occurred; two pts (7%) developed grade 2 IEC-HS (Su, 2023; Srinagesh, 2023). Based on these notable results, this potentially pivotal ph 2 trial has been initiated. Methods: This Phase 2 study will evaluate the safety/efficacy of CRG-022 at 1x10 6 CAR+ T cells/kg in pts with R/R LBCL whose disease has progressed after CD19-directed CAR T-cell therapy. The primary endpoint is ORR according to Lugano response criteria (Cheson, 2014) by blinded independent review. Adverse events (AEs) are graded per CTCAE v5 except with CRS, ICANS, and IEC-HS graded per ASTCT guidelines. Pts with diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, DLBCL transformed from follicular or marginal zone lymphoma, follicular large B-cell lymphoma (FLBL)/FL Grade 3B, and primary mediastinal B-cell lymphoma are eligible. Other eligibility criteria include adequate hematologic and organ function, and no prior allogeneic stem cell transplant. Pts with prior treatment to both a CD19-directed auto CAR-T and a bispecific T-cell engaging antibody are also eligible within a separate cohort. Lymphodepletion with fludarabine 30 mg/m 2 /day and cyclophosphamide 500 mg/m 2 /day for 3 days will be administered ahead of a single infusion of CRG-022. The study is designed to enroll approximately 123 pts. Study enrollment commenced in the US in August 2023, with 9 pt infused as of 08 JAN 2024. Clinical trial information: NCT05972720 .
Details
- Title: Subtitle
- Phase 2 open label, multicenter study evaluating CRG-022, a CD22-directed autologous CAR T-cell therapy, in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) after CD19-directed CAR T-cell therapy
- Creators
- Armin Ghobadi - Washington University in St. LouisCaron Alyce Jacobson - Dana-Farber Cancer InstituteJoseph McGuirk - University of Kansas Medical CenterNirali Shah - National Institutes of HealthJohn Rossi - Cargo Therapeutics, San Carlos, CATonia Jane Buchholz - CARGO Therapeutics, San Carlos, CALizamarie Bachier-Rodriguez - The Blood and Marrow Transplant Group of GA, Atlanta, GAJohn H. Baird - City Of Hope National Medical CenterCatherine S. Diefenbach - NYU Langone HealthUmar Farooq - University of IowaFrancisco J. Hernandez-Ilizaliturri - Roswell Park Comprehensive Cancer CenterIris Isufi - Yale UniversityKrish Patel - Center for Cancer and Blood DisordersSattva Swarup Neelapu - The University of Texas MD Anderson Cancer CenterCraig Steven Sauter - Cleveland ClinicJay Y. Spiegel - University of MiamiMichael Timothy Tees - Colorado Blood Cancer InstituteJohn Timmerman - University of California, Los AngelesGinna Laport - CARGO Therapeutics, San Carlos, CAMatthew Joshua Frank - Stanford University
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.42(16_suppl), pp.TPS7085-TPS7085
- DOI
- 10.1200/JCO.2024.42.16_suppl.TPS7085
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 06/01/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984649038902771
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