UCART19 / Allogene Therap, Cellectis, Pfizer, Servier - LARVOL DELTA

CD-19 CAR-T cell therapy in adult B-cell ALL patients: A systematic review of clinical trials. (ASCO 2025) - "CD19 CAR-T cell therapies, including Obe-cel, KTE-X19, UCART19, and GC007g, have demonstrated efficacy and safety in the treatment of relapsed/refractory (RR) adult B-cell ALL patients. Among these, Obe-cel stands out with a lower incidence of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), making it a promising therapy for outpatient administration. However, large-scale, randomized, multi-center clinical trials are essential to validate these findings and further refine the role of CD19 CAR-T therapies in this high-risk population."

CAR T-Cell Therapy • Clinical • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Addressing graft-versus-host disease in allogeneic cell-based immunotherapy for cancer. (PubMed, Exp Hematol Oncol) - "Clinical trials evaluating these strategies, such as UCART19 and CTX110, demonstrate promising results in preventing GvHD while maintaining anti-tumor efficacy. The review also addresses manufacturing considerations for allogeneic cell products and the challenges in translating preclinical findings into clinical success. By addressing these challenges, allogeneic cell-based immunotherapy continues to advance, paving the way for more accessible, scalable, and effective cancer treatments."

Journal • Review • Gene Therapies • Graft versus Host Disease • Immunology • Oncology

A Study to Evaluate the Long-term Safety of Patients With Advanced Lymphoid Leukemia Who Have Been Previously Administered With UCART19 (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Feb 2025 ➔ Sep 2028 | Trial primary completion date: Feb 2025 ➔ Sep 2028

Trial completion date • Trial primary completion date • Hematological Malignancies • Leukemia • Oncology

EFFICACY OF SALVAGE THERAPY INCLUDING NOVEL AGENTS IN ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA (B-ALL) PROGRESSING AFTER ALLOGENEIC STEM CELL TRANSPLANTATION: A REAL-WORLD UK STUDY (EBMT 2024) - "Historically, intensive salvage therapy was limited to Donor Lymphocyte Infusion (DLI) or second allo-SCT, but more recently, the emergence of novel targeted therapies such as Blinatumomab, Inotuzumab and CAR-T cells have broadened treatment options...17 patients received CAR-T therapy: 4 received UCART19; 1 received dual-targeting CD19/CD22 CAR-T, and 12 received CD19 CAR-T (Kymriah; Obe-cel)... This study highlights the superior outcomes of CAR-T therapy for relapsed B-ALL post allo-SCT, supported by rigorous landmark analysis and propensity matching. The efficacy of 2nd allo-SCT is limited, unless utilized as post-CAR-T consolidation. DLI emerges as a potentially beneficial intervention and its impact should be explored in other datasets to confirm this finding."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD22

EFFICACY OF SALVAGE THERAPY INCLUDING NOVEL AGENTS IN ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA (B-ALL) PROGRESSING AFTER ALLOGENEIC STEM CELL TRANSPLANTATION: A REAL-WORLD UK STUDY (EBMT 2024) - "Historically, intensive salvage therapy was limited to Donor Lymphocyte Infusion (DLI) or second allo-SCT, but more recently, the emergence of novel targeted therapies such as Blinatumomab, Inotuzumab and CAR-T cells have broadened treatment options...17 patients received CAR-T therapy: 4 received UCART19; 1 received dual-targeting CD19/CD22 CAR-T, and 12 received CD19 CAR-T (Kymriah; Obe-cel)... This study highlights the superior outcomes of CAR-T therapy for relapsed B-ALL post allo-SCT, supported by rigorous landmark analysis and propensity matching. The efficacy of 2nd allo-SCT is limited, unless utilized as post-CAR-T consolidation. DLI emerges as a potentially beneficial intervention and its impact should be explored in other datasets to confirm this finding."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD22

SINGLE CENTRE LONG-TERM OUTCOMES OF RELAPSED/REFRACTORY PAEDIATRIC B-ALL AFTER GENOME-EDITED ‘UNIVERSAL’ CAR19 T CELL THERAPY (EBMT 2024) - P1 | " Outcomes of paediatric patients (aged 0.8-16 years) treated at GOS between 2015 and 2022 with either UCART19 (1.1-4.6 x 106) or TT52CAR19 (0.8-2.0 x 106) CAR19 T cells/kg cells were surveyed...Our GOS augmented lymphodepletion (ALD) protocol comprising (total doses) fludarabine 150 mg/m2, cyclophosphamide 120 mg/kg, and alemtuzumab 1 mg/kg was used in 12/15 children... Longer term data for children treated at a single centre with genome-edited allogeneic CAR19 T cells indicate sustained remission in patients transplanted in molecular (PCR) MRD remission. Overall survival at our centre has been comparable to the wider autologous CAR19 setting, despite multiple lines of previous therapy, including CARs, Bi-specific T-cell engagers (BiTEs) and previous transplant. Notably, surviving subjects had all received augmented lymphodepletion ahead of CAR19 T cells, highlighting the importance of addressing host mediated barriers to mismatched cells for deep and rapid leukemic..."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Pediatrics • Transplantation • CD4 • CD52

Efficacy of CAR-T Cells for Post-Transplant Relapsed Adult B-ALL (EBMT-EHA 2024) - "17 patients received CAR-T therapy: UCART19(n=4); CD19/CD22 CAR-T(n=1), CD19CAR-T (Kymriah; Obe-cel) (n=12). 75 patients received non-CAR-T therapies: TKI (n=24), Blinatumumab (n=11), Inotuzumab (n=12), Intensive chemotherapy (n=10), Intensive Chemotherapy and TKI (n=3), palliative/supportive regimens (n=14), and allo-HCT (n=1)... In the context of numerous innovative targeted therapies for B-ALL, CAR-Ts have now, for the first time, exhibited superior outcomes over alternative approaches in post-transplant relapsed B-ALL. More patients in this setting should be offered CAR-T therapy as salvage therapy post-HCT. Clinical Trial Registry: ."

CAR T-Cell Therapy • Clinical • Post-transplantation • Acute Lymphocytic Leukemia • Palliative care • Transplantation • CD22

An "Off-the-Shelf" CD2 Universal CAR-T Therapy Combined with a Long-Acting IL-7 for T-Cell Malignancies (ASH 2023) - "To determine the impact of CD2 antigen loss on CAR-T cell function, CRISPR-mediated CD2 KO was performed in CD19 targeting CAR-T cells (UCART19ΔCD2). We have developed an allogenic "universal" CD2-targeting CAR-T cell UCART2, which is effective against T-ALL and CTCL/T-NHL. We found that CD2 deletion in CAR-T cells resulted in reduced secretion of effector cytokines and reduced anti-tumor activity in vivo, indicating that CD2 is critical for CAR-T function. However, when combined with rhIL-7-hyFc (efineptakin alfa), a long-acting recombinant IL-7, UCART2 induced durable complete responses in both primary and tumor rechallenge experiments in vivo."

Cutaneous T-cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CD2 • GZMB • IFNG • IL7

An "off-the-shelf" CD2 universal CAR-T therapy for T-cell malignancies. (PubMed, Leukemia) - "To evaluate the impact of CD2 on CAR-T function, we generated CD19 CAR-T cells (UCART19) with or without CD2 deletion, single-cell secretome analysis revealed that CD2 deletion in UCART19 reduced frequencies of the effector cytokines (Granzyme-B and IFN-γ). Treatment with rhIL-7-hyFc prolonged UCART2 persistence and increased survival in both the tumor re-challenge model and primary patient T-ALL model in vivo. Together, these data suggest that allogeneic fratricide-resistant UCART2, in combination with rhIL-7-hyFc, could be a suitable approach for treating T-cell malignancies."

Journal • Cutaneous T-cell Lymphoma • Graft versus Host Disease • Immunology • Oncology • T Acute Lymphoblastic Leukemia • CD2 • GZMB • IFNG

A Study to Evaluate the Long-term Safety of Patients With Advanced Lymphoid Leukemia Who Have Been Previously Administered With UCART19 (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Hematological Malignancies • Leukemia • Oncology

Cellectis Publishes Article in Frontiers in Immunology Unveiling Pre-Clinical Data on a Novel Treatment Paradigm for Successful CAR T Immunotherapy Against Stroma-rich Solid Tumors (GlobeNewswire) - "Cellectis...published an article in Frontiers Bioenginnering, demonstrating the efficacy of its TALEN® engineered FAP UCART-cells in cancer-associated fibroblast (CAF) depletion, reduction of desmoplasia and tumor infiltration....In a mouse xenograft model, successful implantation of injected CAFs in the tumors was confirmed by positive staining of spindle-like cells with human-specific FAP antibody, recapitulating a physiologically relevant TNBC tumor with tumor and stromal compartments. FAP UCART-cells alone significantly reduced tumor growth."

Preclinical • Oncology • Solid Tumor

UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial. (PubMed, Lancet Haematol) - P1 | "UCART19 had a manageable safety profile, and showed evidence of antileukaemic activity in heavily pretreated adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. This study shows that allogeneic off-the-shelf CAR T cells can be used safely to treat patients with relapsed B-cell acute lymphoblastic leukaemia."

CAR T-Cell Therapy • Journal • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Leukemia • Oncology

Clinical Pharmacology and Determinants of Response to UCART19, an Allogeneic Anti-CD19 CAR-T Cell Product, in Adult B-cell Acute Lymphoblastic Leukemia. (PubMed, Cancer Res Commun) - "All patients underwent lymphodepletion with fludarabine and cyclophosphamide ± alemtuzumab and received one of three ascending doses of UCART19. These results shed light on the factors associated with UCART19 kinetics, which remain highly affected by the impact of alemtuzumab on IL7 and host-versus-graft rejection. First description of the clinical pharmacology of a genome-edited allogeneic anti-CD19 CAR-T cell product showing the crucial role of an alemtuzumab-based regimen in sustaining UCART19 expansion and persistence through increased IL7 availability and decreased host T lymphocyte population."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Hematological Malignancies • Leukemia • Oncology • Transplant Rejection • IL7

Mechanistic Modeling of the Interplay Between Host Immune System, IL-7 and UCART19 Allogeneic CAR-T Cells in Adult B-cell Acute Lymphoblastic Leukemia. (PubMed, Cancer Res Commun) - "Simulations from the final model recapitulated UCART19 expansion rates in the clinical trial, confirmed the need for alemtuzumab to observe UCART19 expansion (along with fludarabine cyclophosphamide), quantified the importance of allogeneic elimination, and suggested a high impact of multipotent memory T-cell subpopulations on UCART19 expansion and persistence. A mathematical mechanistic pharmacokinetic/pharmacodynamic model supports and captures quantitatively the beneficial impact of lymphodepleting patients before the infusion of an allogeneic CAR-T cell product. Mediation through IL-7 increase and host T lymphocytes decrease is underlined, and the model can be further used to optimize CAR-T cell therapies lymphodepletion regimen."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD19 • IL7

Preliminary Results of UCART19, an Allogeneic Anti-CD19 CAR T-Cell Product in a First-in-Human Trial (PALL) in Pediatric Patients with CD19+ Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (ASH 2017) - P1; "...Lentiviral-transduced CAR T-cells express (1) an anti-CD19 CAR (anti-CD19 scFv- 41BB- CD3ζ), and (2) an RQR8 “safety switch” that is intended to allow targeted elimination of RQR8+ cells by rituximab...The lymphodepletion regimen combines cyclophosphamide and fludarabine with or without alemtuzumab (FC or FCA)...All had received debulking chemotherapy and/or inotuzumab ozogamicin therapy before UCART19...All pts experienced reversible cytokine release syndrome (CRS) (1 grade (G) 1, 3 G2, 1 G3), with one child requiring 2 doses of tocilizumab...Preliminary results of this first-in-human trial of UCART19 treatment in a high risk R/R B-ALL pediatric population revealed no unexpected toxicities. GvHD seen in 2 patients was mild and self-limiting. Lymphodepletion-related viral complications and persisting neutropenia were encountered."

CAR T-Cell Therapy • Clinical • P1 data • Acute Lymphocytic Leukemia • Biosimilar • Cytomegalovirus Infection • Graft versus Host Disease • Venous Thromboembolism

A Study to Evaluate the Long-term Safety of Patients With Advanced Lymphoid Leukemia Who Have Been Previously Administered With UCART19 (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Institut de Recherches Internationales Servier | Active, not recruiting ➔ Recruiting | Trial completion date: Mar 2040 ➔ Feb 2025 | Trial primary completion date: Mar 2040 ➔ Feb 2025

Enrollment open • Trial completion date • Trial primary completion date • Hematological Malignancies • Leukemia • Oncology

"Excited to share publication of UCART19, an allogeneic CD19 CAR-T in B-ALL. @TheLancetHaem 25 pts. Median 4 prior Rx. 72% had prior allo-SCT. Median age 37. CR/CRi 12/25 (48%). Median DOR 7.4 mos. 9/12 responders had subsequent allo-SCT. Median OS 13.4 mos. #leusm #TcellRx" (@NitinJainMD)

Clinical • Hematological Malignancies • Leukemia • CD19

UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial (Lancet Haematol) - P1 | N=25 | CALM (NCT02746952) | "After a median of follow-up of 12·8 months (IQR 2·8–24·8), overall response rate was 48% (95% CI 28–69; 12 of 25 patients), duration of response and median relapse-free survival were 7·4 months (95% CI 1·8 to not calculable), progression-free survival was 2·1 months (95% CI 1·2–2·8), and overall survival was 13·4 months (95% CI 4·8–23·0)....UCART19 had a manageable safety profile, and showed evidence of antileukaemic activity in heavily pretreated adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia."

P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Servier severs CAR-T collab with Allogene, handing back rights outside the US to 3 candidates (FierceBiotech) - "CAR-T therapies targeting CD19 might be considered a hot ticket in biotech, but that hasn’t stopped French pharmaceutical research company Servier from scrapping its collaboration with Allogene Therapeutics. Servier notified the South San Francisco-based company Sept. 15 that it is pulling out of developing the CD19 CAR-Ts the two companies were working on. Of these drugs, UCART19 is in a phase 2 trial for hematological malignancies, while two other candidates-ALLO-501 and ALLO501A-reached phase 1 trials for relapsed/refractory large B-cell lymphoma....With Servier out of the picture, Allogene said in its Securities and Exchange Commission (SEC) filing that it will now pursue licensing these therapies outside the U.S., with potentially an additional 46 million euros ($54.4 million) to come in milestone payments for ALLO-501A."

Licensing / partnership • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellectis to Present Pre-Clinical Data on TALEN-edited Smart CAR T-cells Supporting Improved Solid Tumor Targeting at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting (GlobeNewswire) - "Cellectis...announced today that pre-clinical data on TALEN®-edited smart CAR T-cells to overcome key challenges of targeting solid tumors, will be presented at the Society for Immunotherapy of Cancer’s 37th Annual Meeting (SITC 2022), to be held in Boston, M.A. and virtually on November 8-12, 2022."

Preclinical • Breast Cancer • Oncology • Solid Tumor

THE PRELIMINARY SAFETY AND EFFICACY STUDY OF SC-U02, A NON-VIRAL GENOME TARGETING, ANTI-CD19 UNIVERSAL CAR-T PRODUCT, IN RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS (EHA 2022) - "In this study, we conducted a Non-viral Genome Targeting approach for producing the allogeneic anti-CD19 CAR-T cells (nvGT UCART19), SC-U02...Tocilizumab was administered during CRS for this patient, and the symptom was reversed afterwards...However, due to limited cases reported, SC-U02’s safety and efficacy profile still needs to be decided. The research is ongoing and 6×10 8 cell dose level will be assessed later on."

Clinical • IO biomarker • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B2M • HLA-E • IL6

Antibody Response after One and/or Two Doses of BNT162b2 Anti- Sars-Cov-2 mRNA Vaccine in Patients Treated By CAR T-Cells Therapy (ASH 2021) - "All patients were pretreated for lymphodepletion by fludarabine + cyclophosphamide before CAR-T infusion. The CAR-T provided were axicabtagene ciloleucel (Yescarta, Kite/Gilead, n=16, tisagenlecleucel (Kymriah, Novartis Pharma, n=5 and brexucabtagene autoleucel (KTE-X19, Tecartus, Kite/Gilead, n=1). One additional patient received allogeneic UCART19 (Servier)...The two patients in relapse and treated by chemotherapy or tafasitamab did not develop antibodies after V2 conversely to the patient under maintenance by revlimid... This study shows that the administration of two doses of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine provides a low rate of seroconversion (30%) in recipients of CAR-T therapy. This is likely related to the profound B-cell depletion induced by this treatment precisely targeting CD19+ cells. Investigation of the development of specific T-cell responses in these individuals could provide more information about the efficacy of vaccination in this..."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases • CD19

PHASE I STUDY OF UCART19, AN ALLOGENEIC ANTI-CD19 CAR T-CELL PRODUCT, IN HIGH RISK PEDIATRIC PATIENTS WITH CD19+ RELAPSED/REFRACTORY (R/R) B-CELL ALL: PRELIMINARY RESULTS OF PALL STUDY (EHA 2018) - "...Prior to UCART19 single dose infusion, a lymphodepletion regimen combining high-dose fludarabine-cyclophosphamide, with or without alemtuzumab (FCA or FC) was administered...CRS were manageable by supportive care tocilizumab... UCART19 shows an acceptable safety profile and was able to induce molecular remission in 5 out of 6 patients enabling allogeneic transplantation to proceed. The study is open and recruiting at multiple sites."

CAR T-Cell Therapy • Clinical • P1 data • Hematological Malignancies

UCART19, AN ALLOGENEIC ANTI-CD19 CAR T-CELL PRODUCT, IN HIGH RISK ADULT PATIENTS WITH CD19+ RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: PRELIMINARY RESULTS OF PHASE I CALM STUDY (EHA 2018) - "...A lymphodepletion regimen (cyclophosphamide 1500mg/m and fludarabine 90mg/m with or without alemtuzumab 1mg/kg), was administered prior to UCART19 single dose infusion...Tocilizumab was needed in 5/8 pts... UCART19 shows an acceptable safety profile. 6/9 pts achieved complete remission of which 5 became MRD- enabling a second allo-SCT. Recruitment is ongoing at DL2."

CAR T-Cell Therapy • Clinical • P1 data • Acute Lymphocytic Leukemia

Preliminary Data on Safety, Cellular Kinetics and Anti-Leukemic Activity of UCART19, an Allogeneic Anti-CD19 CAR T-Cell Product, in a Pool of Adult and Pediatric Patients with High-Risk CD19+ Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (ASH 2018) - P1; "...A lymphodepleting regimen (LD) combining cyclophosphamide (1500 mg/m² in CALM, 120 mg/kg in PALL) and fludarabine (90 mg/m2 in CALM, 150 mg/m2 in PALL) without (FC) or with alemtuzumab (FCA) (1 mg/kg) was administered one week before UCART19 infusion on Day 0 (D0)...All pts who achieved MRD- had evidence of UCART19 expansion. Updated data, including data for the highest dose level in CALM study, will be presented (NCT 02746952, NCT02808442)."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Biosimilar • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Neutropenia • Oncology