ssCART-19 / Shanghai Unicar - LARVOL DELTA

EFFICACY AND SAFETY OF CAR-T CELL THERAPY IN B-ALL PATIENTS PREVIOUSLY TREATED WITH BLINATUMOMAB (EBMT 2025) - "Since blinatumomab and CD19 chimeric antigen receptor (CAR)-T cell therapy have similar mechanisms of action, whether prior blinatumomab will affect subsequent CD19 CAR-T cell therapy remains unclear. In this study, we discovered that in patients who had previously received blinatumomab treatment, CAR-T cell therapy remained effective, but the efficacy was reduced compared with blinatumomab-naive patients. Based on the safety profile, the incidence of CRS and ICANS was comparable, and no serious AEs were observed. In conclusion, our findings suggested that the subsequent CD19-targeted therapy after blinatumomab could provide therapeutic benefits to patients with R/R B-ALL."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • CD22

EFFICACY AND SAFETY OF CAR-T CELL THERAPY IN B-ALL PATIENTS PREVIOUSLY TREATED WITH BLINATUMOMAB (EBMT 2025) - "Since blinatumomab and CD19 chimeric antigen receptor (CAR)-T cell therapy have similar mechanisms of action, whether prior blinatumomab will affect subsequent CD19 CAR-T cell therapy remains unclear. In this study, we discovered that in patients who had previously received blinatumomab treatment, CAR-T cell therapy remained effective, but the efficacy was reduced compared with blinatumomab-naive patients. Based on the safety profile, the incidence of CRS and ICANS was comparable, and no serious AEs were observed. In conclusion, our findings suggested that the subsequent CD19-targeted therapy after blinatumomab could provide therapeutic benefits to patients with R/R B-ALL."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • CD22

BCMA CAR-T therapy as salvage therapy in patients with plasmablastic myeloma. (PubMed, Hematology) - "BCMA CAR-T therapy was safe and effective as a salvage treatment for PBM, and its toxicity was controllable. Future research will examine the use of CAR-T therapy as part of combination regimens."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Respiratory Diseases • Transplantation

Safety and Efficacy of CD22/ CD19 CAR-T and Auto-HSCT "Sandwich"Strategy As Consolidation Therapy for Ph Negative B Cell Acute Lymphoblastic Leukemia (ASH 2024) - P1/2 | "Afterwards, autologous CAR T-cells targeting CD22 and CD19 (CAR-T 1, co-stimulatory molecule was 4-1BB and infusion dose was 5×106/kg, respectively) were sequential infused after lymphodepletion chemotherapy with fludarabine and cytophosphamide...Four of 7 relapsed patients received allo-HSCT, 2 relapsed patients who declined allo-HSCT received Blinatumomab, and 1 patient was undergoing the chemotherapy as re-induction treatment...CD22/CD19 CAR-T resulted in deeper remission before transplantation. The new strategy may benefit patients from LFS and OS."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • CD22

Sequential Infusion of Anti-CD19 and Anti-BCMA Chimeric Antigen Receptor T-Cells: A Promising Treatment Strategy for Refractory Immune-Mediated Platelet Transfusion Refractoriness (ASH 2024) - P1/2 | "Refractory iPTR (riPTR), which exhibits resistance to multiple therapeutic plasma exchange, high dose of IgG and rituximab, may result from incomplete elimination of allo-specific B cells and long-lived plasma cells...Methods : In this prospective single-arm clinical trial, patients with riPTR received a combination of murine anti-BCMA CAR T-cells and murine anti-CD19 CAR T-cells at a dose of 2×107 cells/kg...All adverse events were reversible and manageable. Conclusions : CAR T-cell therapy could be well-tolerated and highly effective in overcoming riPTR and eradicating allo-antibodies, making it applicable to antibody-mediated diseases."

CAR T-Cell Therapy • Hematological Disorders • Hematological Malignancies • Infectious Disease • Oncology

5-Year Follow-up of Combined Infusion of Anti-CD19 and Anti-BCMA CAR-T after ASCT for High-Risk Newly Diagnosed Multiple Myeloma (ASH 2024) - "Our preliminary study showed that anti-CD19 and anti-BCMA CAR-T cell therapy followed by lenalidomide maintenance after ASCT yielded encouraging activity for high-risk NDMM...Conclusions : To the best of our knowledge, this is the first clinical trial to incorporate anti-BCMA and anti-CD19 CAR-T cells as consolidation therapy for high-risk NDMM patients...This novel therapeutic strategy shows promise in addressing the unmet needs of high-risk NDMM patients, potentially offering a new direction in the management of this challenging subgroup of multiple myeloma. Further studies are warranted to confirm these encouraging results and to fully elucidate the role of dual-target CAR-T cell therapy in the treatment paradigm for high-risk NDMM."

Hematological Malignancies • Multiple Myeloma • Oncology • IL6

Unleashing the Power of CD19 CAR-T in Relapsed AML: Findings from a Prospective Single-Center Clinical Trial (ASH 2024) - P1/2 | "Following tumor reduction chemotherapy, all patients received a dose-escalated infusion of 5-20 ×106 CD19 CAR-T cells/kg after lymphodepletion chemotherapy with cyclophosphamide (300 mg/m² for 3 days) and fludarabine (30 mg/m² for 3 days) from days -5 to -3. Bone Marrow Transplant. 2019; 54 : 1138-40."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cardiovascular • Hepatology • Hypertension • Liver Failure • Neutropenia • Thrombocytopenia • CD19 • KIT • TP53

Target Antigen-Expressing T Cells Facilitate CAR-T Cell Eradication of Residual CD19+ B Malignant Cells (ASH 2024) - "Underpinned by this hypothesis, we devised an in vitro model to assess target cell dosage and an in vivo mouse model to simulate the clinical situation of minimal residual disease (MRD), which collectively demonstrated that the immune response of anti-CD19 CAR-T cells is reliant on the dosage of the target antigen, with activation occurring only upon reaching a threshold level of target cells...In fact, our recently published phase I/II study has substantiated the therapeutic impact of employing TAET cells in conjunction with CAR-T cells to achieve complete molecular response (CMR)(bloodadvances.2022009072). Furthermore, this combined treatment strategy is highly flexible and scalable, applicable to various targets, target cell types, and effector cell types, to tackle a range of clinical issues."

CAR T-Cell Therapy • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • LAMP1

Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. (PubMed, Hemasphere) - "Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • IL6

The ICANS incidence rate is 0! [Google translation] (Sohu.com) - P1 | N=18 | NCT04825496 | Sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | "ssCART-19 is a new CAR-T product independently developed by Eucardi , the world's first product that combines cutting-edge shRNA gene silencing technology with CAR-T technology. The latest data from its Phase I clinical study was announced at ESMO...It is worth noting that no patient has developed ICANS, and no deaths due to CRS or ICANS have been observed....In terms of efficacy, the overall response rate (ORR) within 3 months reached 87.5% , 10 of the 16 patients achieved complete remission (CR, 62.5%), and 4 patients achieved complete remission with incomplete hematological recovery (CRi, 25.0%). The 6-month sustained remission (DOR) rates of the DL1, DL2, and DL3 groups were 100.0%, 80.0%, and 0.0%, respectively."

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

CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1/2 | N=27 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

High efficacy and safety of interleukin-6-knockdown CD19-targeted CAR-T cells in relapsed/refractory B-ALL patients (ESMO 2024) - P1 | "ssCART-19 achieved a high rate of remission in adult patients with R/R B-cell ALL, it can greatly improve the safety of CAR-T therapy, especially in central nervous system infiltration patients."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Oncology • IL6

CD19 CAR T-cell therapy in relapsed TCF3-HLF-positive B-cell acute lymphoblastic leukemia. (PubMed, Ann Hematol) - No abstract available

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • TCF3

CD19 chimeric antigen receptor-T cells as bridging therapy to allogeneic hematopoietic cell transplantation improves outcome in patients with refractory/relapsed B-cell acute lymphoblastic leukemia. (PubMed, Heliyon) - "In this research we investigated the efficiency and long-term outcomes of CD19 CAR-T bridging with allo-HSCT in R/R B-ALL patients...Moreover, patients who underwent this combined treatment had higher OS and LFS rates compared to those who received CAR-T therapy alone. In conclusion, the results of this clinical trial provide compelling evidence for the safety and efficacy of using CAR-T therapy as a bridging strategy to allo-HSCT in patients with R/R B-ALL."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

HIGH EFFICACY AND SAFETY OF INTERLEUKIN-6-KNOCKDOWN CD19-TARGETED CAR T CELLS IN RELAPSED/REFRACTORY B-ALL PATIENTS (EHA 2024) - P1/2 | "Aims: We compared the efficacy and safety of ssCART-19 to classical CART-19 cells (cCART-19) in patients with r/r B-ALL...All patients received lymphodepleting fludarabine and cyclophosphamideprior to CAR-T cells infusion... ssCART-19 is the first-in-world novel safe CAR-T product that firstly incorporates shRNA gene silencingtechnology to CAR-T technology. Notably, ssCART-19 shows good clinical efficacy and safety in B-ALL patientsincluding CNS-L patients. These clinical findings support the potential of ssCART-19 as a promising therapeuticapproach for r/r B-ALL patients."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • IL6

UniCAR-Therapy Bio’s CAR-T Therapy Granted Breakthrough Status in China (NAVLIN DAILY) - P1/2 | N=50 | NCT03919240 | "Breakthrough therapy designation (BTD) was granted to Shanghai UniCAR-Therapy Bio-Medicine Technology Co., Ltd’s autologous CD19 targeted chimeric antigen receptor (CAR) T-cell therapy, ssCART-19, in China...The candidate, which silences interleukin-6 (IL-6) expression, was designated in refractory/relapsed acute lymphoblastic leukemia (ALL)....In a Phase 1/2 study, ssCART-19 was compared with classic CART-19 cells, which cannot silence IL-6 expression. Among relapsed/refractory B-ALL patients, ssCART-19 demonstrated an improved safety profile, objective response rate (ORR) (91.49% vs 85%), and progression-free survival (PFS) (82.3% vs 66.9%)."

Breakthrough therapy • P1/2 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Clinical Trial of ssCART-19 Cell Injection in the Treatment of Relapsed or Refractory Acute Lymphoblastic Leukemia (Including Central Nervous System Infiltration) (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

New P2 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1/2 | N=27 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Safety and Efficacy of CD22/ CD19 CAR-T and Auto-HSCT "Sandwich" Strategy As Consolidation Therapy for Ph Negative B Cell Acute Lymphoblastic Leukemia (ASH 2023) - P1/2 | "Afterwards, autologous CAR T-cells targeting CD22 and CD19 (CAR-T 1, co-stimulatory molecule was 4-1BB and infusion dose was 5×106/kg, respectively) were sequential infused after lymphodepletion chemotherapy with fludarabine and cytophosphamide...Two patients with Ph- B-ALL relapsed at 5 and 6 months after auto-HSCT and were treated with blinatumomab... Our preliminary study demonstrated that CD22/CD19 CAR-T and Auto-HSCT "Sandwich" strategy as a consolidation strategy showed favorable safety and efficacy in Ph- B-ALL. CD22/CD19 CAR-T resulted in deeper remission before transplantation. The new strategy may benefit patients from LFS and OS."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD22

Efficacy and Safety of the Second CAR-T Therapy in Patients with Refractory/Relapsed Acute B-Cell Lymphoblastic Leukemia (ASH 2023) - "A total of 5 patients with severe cytokine release syndrome (Grade ≥ 3) were observed, including 2 patients in the single CD19 CAR-T group, 2 patients in the tandem CD19/CD22 CAR-T group, and 1 patient in the sequential CD19 and CD22 CAR-T group. Of the 23 patients who achieved CR, 4 patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 3 patients received decitabine (DAC) consolidation.With the median follow-up of 25.5 months (range, 1.1 to 33.5), the 2-year overall survival, leukemia-free survival (LFS) and cumulative incidence of relapse rates were 23.7%, 30.5% and 69.5%, respectively. Multivariate Cox regression analyses showed that a better LFS related to the absence of high-risk cytogenetics and genetic characteristics, DAC combination with fludarabine and cyclophosphamide lymphodepletion regimen, and bridging allo-HSCT or DAC consolidation. Our study showed that the second infusion of tandem CD19/CD22 CAR-T therapy obtains a..."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD22

Phase I Open-Label Single-Arm Study of Sscart-19 in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in China (ASH 2023) - P1 | "Patients received fractionated infusions split over 3 days (10%; 30%; 60%) after lymphodepleting chemotherapy (3 days fludarabine and cyclophosphamide). ssCART-19 CAR-T cell therapy can effectively reduce the incidence of severe CRS and ICANS, especially control the occurrence of ICANS. And ssCART-19 achieved a high rate of remission in adult patients with R/R B-cell ALL. The ORR within 3 months were 83.3%."

Clinical • IO biomarker • P1 data • Acute Lymphocytic Leukemia • Anemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Neutropenia • Oncology • Thrombocytopenia • IL6 • PRF1

Efficacy and Safety of Interleukin-6-Knockdown CD19-Targeted CAR T Cells(ssCART-19) for Relapsed/Refractory B-ALL (ASH 2023) - P1/2 | "In this phase 1/2 clinical trial conducted at two centers, we compared the efficacy and safety of ssCART-19 to classical CART-19 cells (cCART-19) in patients with r/r B-ALL (NCT03919240)...Lymphodepletion (fludarabine at 30 mg/m2/day and cyclophosphamide at 300 mg/m2/day) was conducted on days -5, -4, and -3 before infusion... Our clinical studies demonstrated the safety and high efficacy of ssCART-19 with IL-6 gene silencing in patients with relapsed/refractory B-ALL. These findings support the potential of ssCART-19 as a promising therapeutic approach for this challenging patient population."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • IL2 • IL6 • TNFA

The Clinical Outcome of Patients with Refractory/Relapsed Lymphoid Blastic Phase of Chronic Myeloid Leukemia Treated with CAR T-Cells Therapy (ASH 2023) - "All patients received lymphodepletion with fludarabine (30 mg/m2 /d) and cyclophosphamide (300 mg/m2 /d) -based conditioning regimens on day −5 to −3...Among them, 8 patients with CML-LBC and 92 ph+ ALL patients received single CD19 CAR T therapy, others received tandem CD19/CD22 CAR T. The baseline characteristics of all patients were shown in Table 1... Worser sustained antitumor efficacy and long-term survival with CAR T-cells therapy in patients with CML-LBC compared to ph+ ALL patients, and ABL kinase region mutation is an independent risk factor for CR and LFS."

CAR T-Cell Therapy • Clinical • Clinical data • IO biomarker • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • CD22

CAR-T Therapy for Central Nervous System B-cell Acute Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Feb 2024 ➔ Dec 2025 | Trial primary completion date: Aug 2023 ➔ Dec 2024

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

Humanized CD19 CAR-T Cells With CRS Suppression Technology for r/r CD19+ Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Sep 2024 ➔ Dec 2025 | Trial primary completion date: Sep 2023 ➔ Dec 2024

CAR T-Cell Therapy • Cytokine release syndrome • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology