huCART19 / Novartis, University of Pennsylvania - LARVOL DELTA

Humanized CD19 chimeric antigen receptor (CAR) T-cell therapy for high-risk and post-CAR relapse of B-cell acute lymphoblastic leukemia (ASH 2025) - P2 | "Patients received huCART19 at a dose of 5x106 CAR T cells/kg (maximum 2.5x108) afterlymphodepletion (LD) with fludarabine and cyclophosphamide...Prior therapy included HSCT in 21%, blinatumomab in 21% and inotuzumab in 15%.The CAR-naïve cohort (n=52) included 25 with first early BM relapse within 36m of diagnosis (12 25% blasts, 25/52 (48%) <0.01%...There was 1 death prior to day 28, due to gastrointestinal hemorrhageon day 2 in the setting of progressive ALL and Gr 2 CRS. CAR neurotoxicity was reported in 14/52 (27%, 2Gr 3, 2 Gr 4) CAR-naïve patients and 7/48 (15%, 1 Gr 3, 1 Gr 4) CAR-exposed, with 1 case of Gr 3 cerebraledema, fully recovered, and 1 case of ongoing myelopathy.ConclusionsHuCART19 produced durable remissions in high risk r/r B-ALL and demonstrated efficacy as salvagetherapy for those with poor response to prior CAR therapy, comparing favorably to historical outcomes inthis extremely high risk group."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia

Cost-Effective Manufacture and Promising Initial Efficacy of huCART19 Cells Manufactured Using the Clinimacs Prodigy Platform (ASH 2024) - P1/2 | "After fludarabine/cyclophosphamide lymphodepletion, pts were infused with Prodigy-manufactured huCART19 cells. This trial shows feasibility of manufacturing 4-1BB cells on the Prodigy cost-effectively, with successful manufacture for each pt and all products meeting release criteria. Investigation will continue into the significance of NGS-MRD positivity following Prodigy-manufactured huCART19 therapy, durability of remission, and potentially faster automated GMP manufacturing."

Clinical • Cost effectiveness • HEOR • Bone Marrow Transplantation • CNS Disorders • Epilepsy • Inflammation • Pediatrics

ACADEMIC DEVELOPMENT OF A LENTIVIRAL VECTOR VS CD19 FOR THE TRANSDUCTION OF CHIMERIC T LYMPHOCYTES. PRECLINICAL STAGE. IS IT POSSIBLE IN A MIDDLE INCOME (SIOP 2025) - "Extracellular domain that we will use corresponds to mouse monoclonal antibody that recognizes human CD19 from tisagenlecleucel®. It is feasible to develop a huCART-19 with research grade in Mexico, future would evaluate its function in clinical model."

IO biomarker • Preclinical • Viral vector • Hematological Malignancies • Leukemia • Pediatrics • CD8

Retreatment With CTL019/CTL119 (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: University of Pennsylvania | Trial completion date: Jul 2027 ➔ Jul 2028 | Trial primary completion date: Jul 2027 ➔ Jul 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PREGNANCY AND INFANT OUTCOMES POST–CD19-DIRECTED CAR-T THERAPY: TISAGENLECLEUCEL (TISA-CEL) AND/OR HUCAR19 (CTL119) (EHA 2025) - "Pregnancy and delivery of a healthy infant after CD-19 directed CAR-T therapy is possible. The use of CAR-T therapy, earlier in the pt journey, may improve chances of healthy pregnancy by avoiding the risks for infertility associated with high-dose chemotherapy and/or radiation. Capturing data on all pregnancies post-CAR-T remains an important goal."

IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infertility • Leukemia • Oncology • Pediatrics • Sexual Disorders

Pregnancy and infant outcomes post–CD19-directed CAR-T therapy: Tisagenlecleucel (tisa-cel) and/or huCAR19 (CTL119). (ASCO 2025) - "Pregnancy and delivery of a healthy infant after CAR-T therapy is possible. The use of CAR-T therapy may improve chances of healthy pregnancy by avoiding the risks for infertility associated with high-dose chemotherapy and/or radiation. Capturing data on all pregnancies post CAR-T remains an important goal."

IO biomarker • Acute Lymphocytic Leukemia • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Infertility • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sexual Disorders

Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL (clinicaltrials.gov) - P2 | N=106 | Completed | Sponsor: University of Pennsylvania | Active, not recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ Apr 2024 | Trial primary completion date: Aug 2024 ➔ Apr 2024

Trial completion • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD19

CAR-T Cell Therapy for Desensitization in Kidney Transplantation (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Renal Disease • Transplantation • HLA-B • HLA-C • HLA-DRB1

CAR-T Cell Therapy for Desensitization in Kidney Transplantation (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Mar 2024 ➔ May 2024

CAR T-Cell Therapy • Trial initiation date • Chronic Kidney Disease • Renal Disease • Transplantation • HLA-B • HLA-C • HLA-DRB1

Reinfusion of CD19 CAR T Cells for Relapse Prevention and Treatment in Children with Acute Lymphoblastic Leukemia. (PubMed, Blood Adv) - "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-positive relapse."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Inflammation • Leukemia • Oncology

Co-administration of CART22-65s and huCART19 for B-ALL (clinicaltrials.gov) - P1/2 | N=93 | Recruiting | Sponsor: Stephan Grupp MD PhD | Trial completion date: Jan 2026 ➔ Jan 2029 | Trial primary completion date: Jan 2025 ➔ Jan 2027

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD22

Autologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy) (clinicaltrials.gov) - P1/2 | N=89 | Recruiting | Sponsor: Stephan Grupp MD PhD | Trial completion date: Sep 2027 ➔ Sep 2029 | Trial primary completion date: Sep 2025 ➔ Sep 2027

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • CD19

Autologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy) (clinicaltrials.gov) - P1/2 | N=89 | Recruiting | Sponsor: Stephan Grupp MD PhD | Active, not recruiting ➔ Recruiting | Trial primary completion date: Sep 2023 ➔ Sep 2025

CAR T-Cell Therapy • Enrollment open • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • CD19

CAR-T Cell Therapy for Desensitization in Kidney Transplantation (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

CAR T-Cell Therapy • New P1 trial • Chronic Kidney Disease • Renal Disease • Transplantation • HLA-B • HLA-C • HLA-DRB1

Autologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy) (clinicaltrials.gov) - P1/2 | N=89 | Active, not recruiting | Sponsor: Stephan Grupp MD PhD | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • CD19

Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: University of Pennsylvania | Recruiting ➔ Active, not recruiting | N=63 ➔ 100

Enrollment change • Enrollment closed • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD19

Anti-CD19 CAR T Cells in Combination with Ibrutinib for the Treatment of Chronic Lymphocytic Leukemia. (PubMed, Blood Adv) - P1 | "In CLL patients not achieving a CR despite at least 6 months of ibrutinib, adding huCART-19 mediated a high rate of deep and durable remissions. ClinicalTrials.gov number, NCT02640209."

CAR T-Cell Therapy • Combination therapy • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Inflammation • Leukemia • Oncology

Dual CAR T-Cell for ALL (SOHO 2022) - P1, P1/2 | "Quantitative PCR data demonstrated that CART22-65s and huCART19 had different peak expansions that correlated with distinct cytokine release syndrome events...Early results have demonstrated manufacturing feasibility and anti-leukemia activity; however, limited dual functionality has been observed in some products. Longer follow-up and additional studies are needed to ascertain remission durability and to further optimize dual-targeted CARs."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22

Co-administration of CART22-65s and huCART19 for B-ALL (clinicaltrials.gov) - P1/2 | N=93 | Recruiting | Sponsor: Stephan Grupp MD PhD | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD19 • CD22 • CRP

Academic Development of a Lentiviral Vector vs CD19 (EHA-EBMT-CART 2023) - "The extracellular domain that we will use corresponds to the mouse monoclonal antibody that recognizes human CD19 from tisagenlecleucel®. It is feasible to develop a huCART-19 with research grade in Mexico, the next step is to evaluate its function in a clinical model."

IO biomarker • Viral vector • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD19 • CD8 • TNFRSF9

Co-administration of CART22-65s and huCART19 for B-ALL (clinicaltrials.gov) - P1/2 | N=93 | Not yet recruiting | Sponsor: Stephan Grupp MD PhD

CAR T-Cell Therapy • New P1/2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD19 • CD22 • CRP

Anti-BCMA/CD19 CAR T cells with early immunomodulatory maintenance for multiple myeloma responding to initial or later-line therapy. (PubMed, Blood Cancer Discov) - "We conducted a phase 1 clinical trial of anti-BCMA CAR 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. 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 multiple myeloma treatment."

CAR T-Cell Therapy • Journal • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • CD19

Outcomes after Reinfusion of CD19-Specific Chimeric Antigen Receptor (CAR)-Modified T Cells in Children and Young Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (ASH 2021) - P1, P1/2 | "Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may prolong B-cell aplasia in patients with short CAR persistence and reduce relapse risk, and can induce remissions in patients with CD19+ relapsed disease. Thus, reinfusion may provide an alternative to HSCT for short persistence. However, reinfusion is not effective for patients with nonresponse to initial CAR infusion."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Critical care • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD19

Autologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy) (clinicaltrials.gov) - P1/2 | N=89 | Recruiting | Sponsor: Stephan Grupp MD PhD | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • CD19

"Busy day!! Submitted a manuscript today, resubmitted an #rstats package to CRAN with @Richard_S_Hanna, running a site initiation visit with @GruppSteve and @BarzLeahy for our huCART19 trial, and flying out to Boston for #redcapcon!" (@StephanKadauke)