Delving into the Latest Updates on CTL-119 with Synapse

Overview

Basic Info

Drug Type

Autologous CAR-T

Synonyms

Anti-CD19 CAR-T cell therapy - Novartis/University of Pennsylvania, HUCART19

+ [2]

Target

CD19

Action

modulators

Mechanism

CD19 modulators(B-lymphocyte antigen CD19 modulators), T lymphocyte replacements

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Pre B-cell acute lymphoblastic leukemiaAdult Lymphoblastic LymphomaB lymphoblastic leukemia lymphoma+ [3]

Inactive Indication

CD19 Positive B-Cell Chronic Lymphocytic LeukemiaChronic lymphocytic leukaemia refractoryDiffuse Large B-Cell Lymphoma+ [1]

Originator Organization

Novartis Pharma AG

Active Organization

Novartis AG

The Children's Hospital of Philadelphia

University of Pennsylvania

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Sequence Code 119909co-stimulatory domain

Sequence Code 163267CAR construct

Sequence Code 133244

This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 3 months - 29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.

Start Date18 Jan 2019

Sponsor / Collaborator

University of Pennsylvania

[+1]

100 Clinical Results associated with CTL-119

Login to view more data

100 Translational Medicine associated with CTL-119

Login to view more data

100 Patents (Medical) associated with CTL-119

Login to view more data

7

Literatures (Medical) associated with CTL-119

14 May 2024·Blood Advances

Reinfusion of CD19 CAR T cells for relapse prevention and treatment in children with acute lymphoblastic leukemia

Article

Author: Gonzalez, Vanessa E. ; Fraietta, Joseph A. ; June, Carl H. ; Wray, Lisa ; McGuire, Regina ; Li, Yimei ; Baniewicz, Diane ; Grupp, Stephan A. ; Lawrence, Sophie ; Devine, Kaitlin ; Hunger, Stephen P. ; Kulikovskaya, Irina ; Rheingold, Susan R. ; Aplenc, Richard ; Wertheim, Gerald B. ; Callahan, Colleen ; Leahy, Allison Barz ; Maude, Shannon L. ; Vernau, Lauren ; Liu, Hongyan ; Myers, Regina M. ; Kadauke, Stephan ; DiNofia, Amanda M.

AbstractRelapse after CD19-directed chimeric antigen receptor (CAR)–modified T cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of or treat relapsed disease after initial CAR T-cell infusion (CARTi). We conducted a retrospective review of reinfusion of murine (CTL019) or humanized (huCART19) anti–CD19/4-1BB CAR T cells across 3 clinical trials or commercial tisagenlecleucel for relapse prevention (peripheral B-cell recovery [BCR] or marrow hematogones ≤6 months after CARTi), minimal residual disease (MRD) or relapse, or nonresponse to CARTi. The primary endpoint was complete response (CR) at day 28 after CARTr, defined as complete remission with B-cell aplasia. Of 262 primary treatments, 81 were followed by ≥1 reinfusion (investigational CTL019, n = 44; huCART19, n = 26; tisagenlecleucel, n = 11), representing 79 patients. Of 63 reinfusions for relapse prevention, 52% achieved CR (BCR, 15/40 [38%]; hematogones, 18/23 [78%]). Lymphodepletion was associated with response to CARTr for BCR (odds ratio [OR], 33.57; P = .015) but not hematogones (OR, 0.30; P = .291). The cumulative incidence of relapse was 29% at 24 months for CR vs 61% for nonresponse to CARTr (P = .259). For MRD/relapse, CR rate to CARTr was 50% (5/10), but 0/8 for nonresponse to CARTi. Toxicity was generally mild, with the only grade ≥3 cytokine release syndrome (n = 6) or neurotoxicity (n = 1) observed in MRD/relapse treatment. Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19+ relapse.

01 Mar 2023·Blood Cancer Discovery

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy

Article

Author: Ferthio, Regina ; Koterba, Natalka ; Mansfield, Keith G. ; Carreno, Beatriz M. ; Young, Regina M. ; Miao, Fei ; Cohen, Adam D. ; Lancaster, Eric ; Plesa, Gabriela ; Wilson, Wesley V. ; Gonzalez, Vanessa E. ; Gupta, Minnal ; Linette, Gerald P. ; Hexner, Elizabeth O. ; Lacey, Simon F. ; June, Carl H. ; Bu, Dexiu ; Stadtmauer, Edward A. ; Siegel, Don L. ; Patchin, Margaret ; Four, Megan ; Vogl, Dan T. ; Brogdon, Jennifer L. ; Nelson, Anne Marie ; Kulikovskaya, Irina ; Cosey, Angela ; Leskowitz, Rachel ; Garfall, Alfred L. ; Bartoszek, Robert L. ; Waxman, Adam J. ; Chen, Fang ; Susanibar-Adaniya, Sandra P. ; Fraietta, Joseph A. ; Shea, Kim-Marie ; Brennan, Andrea ; Xu, Rong ; Milone, Michael C. ; Hwang, Wei-Ting ; Tian, Lifeng

AbstractWe conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)–negative complete response/stringent complete response. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T-cell reexpansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T-cell therapy in early lines of MM treatment.Significance:CAR T cells in early lines of MM therapy could be safer and more effective than in the advanced setting, where prior studies have focused. We evaluated the safety, pharmacokinetics, and efficacy of CAR T cells in patients with low disease burden, responding to current therapy, combined with standard maintenance therapy.This article is highlighted in the In This Issue feature, p. 101

08 Nov 2022·Blood AdvancesQ2 · MEDICINE

Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia

Q2 · MEDICINE

Article

Author: Mato, Anthony R. ; Porter, David L. ; Vides, Vanessa ; Lamontagne, Anne ; Frey, Noelle V. ; Melenhorst, J. Joseph ; June, Carl H. ; Byrd, John C. ; Hexner, Elizabeth O. ; O'Brien, Megan ; Gill, Saar ; Gladney, Whitney L. ; Siegel, Donald L. ; Brogdon, Jennifer L. ; Pequignot, Edward ; Fraietta, Joseph A. ; Levine, Bruce L. ; Metzger, Susan ; Davis, Megan M. ; Lacey, Simon F. ; Maus, Marcela V. ; Shestov, Maksim ; Schuster, Stephen J. ; Ruella, Marco ; Hwang, Wei-Ting ; Gaymon, Avery L.

AbstractIn chronic lymphocytic leukemia (CLL) patients who achieve a complete remission (CR) to anti-CD19 chimeric antigen receptor T cells (CART-19), remissions are remarkably durable. Preclinical data suggesting synergy between CART-19 and the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib prompted us to conduct a prospective single-center phase 2 trial in which we added autologous anti-CD19 humanized binding domain T cells (huCART-19) to ibrutinib in patients with CLL not in CR despite ≥6 months of ibrutinib. The primary endpoints were safety, feasibility, and achievement of a CR within 3 months. Of 20 enrolled patients, 19 received huCART-19. The median follow-up for all infused patients was 41 months (range, 0.25-58 months). Eighteen patients developed cytokine release syndrome (CRS; grade 1-2 in 15 of 18 subjects), and 5 developed neurotoxicity (grade 1-2 in 4 patients, grade 4 in 1 patient). While the 3-month CR rate among International Working Group on CLL (iwCLL)-evaluable patients was 44% (90% confidence interval [CI], 23-67%), at 12 months, 72% of patients tested had no measurable residual disease (MRD). The estimated overall and progression-free survival at 48 months were 84% and 70%, respectively. Of 15 patients with undetectable MRD at 3 or 6 months, 13 remain in ongoing CR at the last follow-up. In patients with CLL not achieving a CR despite ≥6 months of ibrutinib, adding huCART-19 mediated a high rate of deep and durable remissions. ClinicalTrials.gov number, NCT02640209.

100 Deals associated with CTL-119

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Adult Lymphoblastic Lymphoma	Phase 2	United States	The Children's Hospital of Philadelphia	25 Jan 2023
B lymphoblastic leukemia lymphoma	Phase 2	United States	The Children's Hospital of Philadelphia	25 Jan 2023
Recurrent B Acute Lymphoblastic Leukemia	Phase 2	United States	The Children's Hospital of Philadelphia	25 Jan 2023
Pre B-cell acute lymphoblastic leukemia	Phase 2	United States	University of Pennsylvania	18 Jan 2019
Refractory Adult Acute Lymphoblastic Leukemia	Phase 1	United States	University of Pennsylvania	27 Sep 2018
Relapse multiple myeloma	Phase 1	United States	Novartis AG	09 May 2018
Relapse multiple myeloma	Phase 1	United States	University of Pennsylvania	09 May 2018
CD19 Positive B-Cell Chronic Lymphocytic Leukemia	Phase 1	United States	University of Pennsylvania	29 Jan 2016
Chronic lymphocytic leukaemia refractory	Phase 1	United States	University of Pennsylvania	29 Jan 2016
Diffuse Large B-Cell Lymphoma	Discovery	United States	University of Pennsylvania	25 Mar 2014

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02640209 (Pubmed \| Blood Adv) Manual	Phase 1	Chronic Lymphocytic Leukemia	19	CTL-119+Ibrutinib	(iqhgafaugw) = 18pts cytokine release syndrome (CRS; grade 1-2 in 15pts) and 5pts neurotoxicity (grade 1-2 in 4pts, grade 4 in 1pt) ajcukhroso (eilkrnlqsi )	Positive	29 Mar 2022