CAR-T CD19/CD20/CD22/CD30 / Shanghai Unicar - LARVOL DELTA

Cellular Kinetics of CD19 Chimeric Antigen Receptor T Cells in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma (ASH 2019) - P2; "CART cells were administrated at doses of 5-10x106/kg in 3 split doses following lymphodepleting chemotherapies of fludarabine and cyclophosphamide. This is the first summary of CD19-41BBζ CART against r/r NHL emphasizing different kinetic profiles between NHL and ALL/CLL. These results also imply that means to enhance long-term persistence of CART cells may be potential strategies of to improve response rates."

CAR T-Cell Therapy • Clinical • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] COMBINED INFUSION OF ANTI-CD19 AND ANTI-BCMA CAR-T CELLS AFTER ASCT IN THE FRONT LINE WAS SUPERIOR TO SINGLE ASCT FOR HIGH RISK MM (EHA 2020) - "Our previous study showed good response for the de novo high risk patients who received CD19 and BCMA-specific CAR-T cell therapy after ASCT in the front line with mild CRS and other side effects (reported on the 2018 ASH meeting)...Study intervention in this clinical trial consisted of 4 cycles of bortezomib-based induction treatment followed stem cell mobilization by cyclophosphamide 3 g/m2...CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused directly on d14 to d20 after transplantation...The median PFS and OS of the patients in two groups were all not reached but 21-months PFS was 73% and 55% for two groups respectively (p<0.05); 21-months OS was 100% and 61% for each group (p<0.05) (Figure 1). Conclusion Combined infusion of anti-CD19 and anti-BCMA CART cells after ASCT for high risk MM was safe and effective, and can significantly prolong the PFS and OS compared to single ASCT."

CAR T-Cell Therapy • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD8 • TNFRSF4

A Study of CD19/22 CART Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Lymphoma (clinicaltrials.gov) - P2; N=20; Recruiting; Sponsor: The First Affiliated Hospital of Soochow University

Clinical • New P2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Study of BiRd Regimen Combined With BCMA CAR T-cell Therapy in Newly Diagnosed Multiple Myeloma (MM) Patients (clinicaltrials.gov) - P3; N=30; Recruiting; Sponsor: The First Affiliated Hospital of Soochow University

CAR T-Cell Therapy • Clinical • New P3 trial

Sequential CD19- and Bcma-Specific Chimeric Antigen Receptor T Cell Treatment for RRMM: Report from a Single Center Study (ASH 2019) - "After one month from CARTs infusion, some pts were adminstrated IMiDs for maintence therapy after hematopoietic recovery, including oral thalidomide 50mg/d or lenalidomide 10mg/d. Combined sequential administration of CART-19 and CART-BCMA cells can be manufactured from heavily-treated MM pts, and could elicit sustained remission for RRMM pts. Toxicities can be well tolerated. CARTs early expansion and persistence in vivo post infusion may be predictive of clinical outcome."

CAR T-Cell Therapy • Clinical • IFNG • IL10 • IL6

Successful Treatment of Chimeric Antigen Receptor T Cell Therapy in Refractory or Relapsed Acute Leukemia Patients with TP53 alterations (ASH 2019) - "After leukapheresis, all patients received fludarabine-based lymphodepletion chemotherapy with FLAG regimen (Fludarabine 30mg/m2 × 5d, Cytarabine 2g/m2 × 5d and Granulocyte-colony stimulating factor 300ug ×6d) in two cases, FC regimen (Fludarabine 30mg/m2 × 3d and Cyclophosphamide 300mg/m2 × 3d) in five cases, and FC+DAC regimen (Decitabine 50mg × 3d, Fludarabine 30mg/m2 × 3d and Cyclophosphamide 300mg/m2 × 3d) in four cases. Our trial indicates that CAR-T therapy is a safe and powerful salvage approach to R/R AL patients with TP53 alterations and application of decitabine may fuel CAR-T therapy and reduce the relapse rate without increasing therapy related mortality incidences in this high risk population."

CAR T-Cell Therapy • Clinical • IO Biomarker • IL6 • TP53

Tandem CAR T Cells Targeting CD19 and CD22 Is a Safe and Highly Efficacious Treatment for Relapse/ Refractory ALL Patients (ASH 2019) - "Only one patient presented MAH syndrome and was cured with low dose dexamethasone. The tandem CD19/CD22 dual target CAR T cells therapy is a safe and high efficacy treatment for R/R ALL patients. It is possible that multi-targeted CAR-T cell therapy may overcome this resistance mechanism and improve clinical outcomes."

CAR T-Cell Therapy • Clinical • IO Biomarker • CD8 • TP53

shRNA-Interleukin-6 Modified CD19-Specific Chimeric Antigen Receptor T Cell Significantly Improves the Safety in Acute Lymphoblastic Leukemia (ASH 2019) - "Tocilizumab was given to 66.7 % (4/6) of the patients in the regular CART-19 cohort and two patients needed more than one treatment with tocilizumab. There was no CAR T-related death. [Conclusion] Our study demonstrated that inhibition of CAR-T derived IL-6 expression by shRNA interfering technology could significantly reduce the severe CRS incidence without affecting their immune-oncotherapy efficacy in treating r/r B-ALL patients, which may provide a potential technology to improve the safety profile and promote the extended use of the CAR-T therapy without sacrificing efficacy."

CAR T-Cell Therapy • Clinical • IO Biomarker • IL6

Combined Infusion of Anti-CD19 and Anti-Bcma CART Cells after Early or Later Transplantation in the Front Line Was Superior to Salvage Therapy for High Risk MM (ASH 2019) - "BuCy or Melphalan were used as conditioning, followed by infusion of autologous stem cells. CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused directly on d14 to d20 after transplantation...Tocilizumab was used to treating only one patient with grade 3 CRS... Combined infusion of anti-CD19 and anti-BCMA CART cells after ASCT for high risk MM was safe and effective, especially as conjunction therapy to early or later transplant at front line even with primary resistant disease or early disease progress. For those RRMM patients, CART cell therapy followed by ASCT seems to be better to prolong patients’ PFS than CART treatment alone with FC chemotherapy reported in our another study (NCT 03196414)."

CAR T-Cell Therapy • CD8 • IFNG • IL10 • IL17A • IL2 • IL4 • IL6

CAR-T Cell Therapy Targeting to CD19 for R/R ALL (clinicaltrials.gov) - P1/2; N=50; Recruiting; Sponsor: The First Affiliated Hospital of Soochow University

CAR T-Cell Therapy • Clinical • New P1/2 trial

SUCCESSFUL TREATMENT OF TWO RELAPSED/REFRACTORY T(8;21) ACUTE MYELOID LEUKEMIA PATIENTS BY CD19-DIRECTED CHIMERIC ANTIGEN RECEPTOR T CELLS (EBMT 2019) - " Both patients received lymphodepletion chemotherapy with Decitabine 20mg/m2×5d, Fludarabine 30mg/m2×3d and Cyclophosphamide 300mg/m2×3d (DAC+FC). Our report implicates that CAR-T-19 is a safe and promising approach to managing R/R t(8;21)AML with CD19 expression, and may provide a salvage treatment approach for all AML patients with CD19 expression and benefit a certain population with AML besides B-linage malignancies. Clinical Trial Registry: NA"

CAR T-Cell Therapy • Clinical • IO Biomarker

TANDOM AUTOLOGOUS TRANSPLANTATION AND COMBINED INFUSION OF CD19 AND BCMA-SPECIFIC CHIMERIC ANTIGEN RECEPTOR T CELLS FOR HIGH RISK MM (EBMT 2019) - "Tandom autologous transplantation and combined infusion of CART-19 and CART-BCMA cells could be another choice of consolidation treatment for high risk MM patients. Toxicities to date including CRS and organ function impairment seemed to be mild and reversable. CD19 CAR-T and BCMA CAR-T cells appeared simultaneously in patients' blood after combined infusion even in MRD state."

CAR T-Cell Therapy