SENL-B19 / SenlangBio - LARVOL DELTA

Surface Density of CAR Molecules May Modulate the Kinetics of CAR-T Cells In Vivo (ASH 2019) - P1; "The expression levels of tEGFR and CAR were determined by flow cytometry using the biotinylated-Erbitux, and the CD19-Fc protein and the α-FMC63scFv antibody, respectively...All subjects were preconditioned with fludarabine and cyclophosphamide before 3x105 CAR-T cells/kg infusion... Using the myeloproliferative sarcoma virus enhancer, we have generated a lentivirus vector, 1904B that can express CAR at a lower level on the cell surface, and investigated 1904B CAR-T functions in cell culture, in a mouse model, and in patients. Lower surface expression of CAR was found with reduced cytotoxicity and lower cytokine release of CAR-T in cell culture, but prolonged T cell activity in a mouse model. Human subjects treated with 1904B CAR-T developed fever later and shorter than 1904A, with slower expansion of CAR-T cells."

CAR T-Cell Therapy • IO biomarker • Preclinical • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • IFNG

[VIRTUAL] An Anti-Bcma CAR T-Cell Therapy (C-CAR088) Shows Promising Safety and Efficacy Profile in Relapsed or Refractory Multiple Myeloma (ASH 2020) - P1 | "C-CAR088 is administered to patients as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen...Four patients (19%) received tocilizumab for CRS treatment... The clinical trial results in patients with R/R MM treated with C-CAR088 show a favorable safety profile and promising signs of efficacy. We will continue to evaluate these patients to understand the long-term effect of C-CAR088 in multiple myeloma patients. Clinical trial information: NCT04322292、NCT03815383、NCT03751293、NCT04295018 Research Sponsor: Cellular Biomedicine Group, Inc."

CAR T-Cell Therapy • Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Analysis of Factors Predicting Treatment Response of 254 Patients Who Received CD19-Targeted CAR-T Cell Therapy for Relapsed/Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (B-ALL) (ASH 2019) - P1, P1/2; "The CR rate of patients who received prior either CAR-T or blinatumomab treatment was lower than those who had not (50% vs. 91.53%, p=0.01)...There were no differences in CR between patients age 1-14 yr and >14 yr, patients with or without extramedullary disease (EMD), or patients receiving different chemotherapies between enrollment and CAR-T cells infusion on top of fludarabine and cyclophosphamide (FC) conditioning regimen...Patients who developed severe neurotoxicity (grade 2-4) post CAR-T had higher odds of achieving CR compared to patients with grade 0-1 neurotoxicity [OR=34.796(95%CI 3.232-374.659)]. Conclusions In this analysis, we have observed that significant risk factors for not achieving CR after CD-19 CAR-T therapy include female gender, BM blasts more than 20%, a positive TP53 mutation, treatment with CD28 co-stimulatory domain vs 4-1BB CAR-T product, and mild as opposed to severe CAR-T related neurotoxicity."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Leukemia • Oncology • CD8 • MLL • TP53

[VIRTUAL] Feasibility, and Efficacy of Donor-Derived cd19-Targeted Car t-Cell Therapy in Refractory/Relapsed(r/r)b-Cell Acute Lymphoblastic Leukemia (b-all) Patients (ASH 2020) - P1, P1/2 | "However, CAR T-cells derived from HLA identical siblings can still be considered in our experience, no GVHD occurred in these patients. But the efficacy of CAR T-cells from haploidentical donors was very poor."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Atrial Fibrillation • B Acute Lymphoblastic Leukemia • Cardiovascular • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD19

[VIRTUAL] Significant Long-Term Benefits of CAR T-Cell Therapy Followed By a Second Allo-HSCT for Relapsed/Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (B-ALL) Patients Who Relapsed after an Initial Transplant (ASH 2020) - P1, P1/2 | "All patients received a conditioning regimen of IV fludarabine (30mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single CAR T-cell infusion with a median dose of 3×105 cells/kg (1×105-6×105 cells/kg) in 21 patients...Post CAR-T therapy, all patients bridged into a consolidation second transplantation with conventional myeloablative pre-transplantation conditioning regimens including 15 patients who received total body irradiation-based and 7 patients that received a busulfan-based conditioning regimen. Cyclosporin A, short-term methotrexate, and mycophenolate mofetil were used for GVHD prophylaxis...Conclusions Our study demonstrates that even for R/R B-ALL patients who have relapsed following a first allo-HSCT , an MRD-negative CR status can still be achieved through CAR T-cell cell therapy without increasing CRS or neurotoxicity, making consolidation second allo-HSCT feasible for these patients. CAR T-cell therapy combined..."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD19

Which is better in CD19 CAR-T treatment of r/r B-ALL, CD28 or 4-1BB? A parallel trial under the same manufacturing process. (ASCO 2018) - P1/2; "...KYMRIAH and YESCARTA used 4-1BB and CD28 co-stimulatory signaling domains, respectively... The study illustrates that 4-1BB CAR-T cells show enhanced safety, efficacy, and expansion than CD28 CAR-T cells, suggesting a superior therapeutic strategy in the treatment of relapsed or refractory CD19-positive B-ALL patients."

Acute Lymphocytic Leukemia

Efficacy and Safety of CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy for B-Cell Acute Lymphocytic Leukemia (B-cell ALL) in a Large Cohort Including Patients with Extramedullary Disease(EMD), High Leukemia Burden, BCR-ABL (+) Mutation,TP53 Mutation, and Post-Transplant Relapse (ASH 2018) - P1/2; "...All pts received a conditioning regimen of IV fludarabine (25 mg/m2/day) and cyclophosphamide (250 mg/m2/day) for 3 days before a single infusion of CAR-T cells with a median dose of 1x105 (0.1-10x105) cells/kg...An early and high relapse rate was observed in TP53+ group. Overall, RFS was superior for pts bridging to allo-HSCT after CAR-T treatment than for those receiving CAR-T- treatment only."

Clinical • Acute Lymphocytic Leukemia • Biosimilar • Brain Cancer • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation

A Feasibility and Safety Study of a New CD19-Directed Fast CAR-T Therapy for Refractory and Relapsed B Cell Acute Lymphoblastic Leukemia (ASH 2019) - P1; "All patients received a conditioning regimen of IV fludarabine (30mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single infusion of CAR-T cells...Conclusion This study has demonstrated that FasT CAR-T cells with superior expansion capability and younger/less exhausted phenotypes can be generated rapidly. This first-in-human clinical study showed that FasT CAR-T is safe and highly effective for treating patients with B-ALL."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • IFNG • IL10 • IL2RA • IL6 • PD-1

Anti-CD19/CD22 Dual CAR-T Therapy for Refractory and Relapsed B-Cell Acute Lymphoblastic Leukemia (ASH 2019) - P1; "All pts received conditioning regimen of fludarabine and cyclophosphamide intravenously for 3 consecutive days with doses of 30 mg/m2/day and 250 mg/m2/day, respectively before a single infusion of CAR-T cells...A low toxicity with dose-dependent high CR rate including pts who previously treated with CD19 CAR-T cells were observed. Longer observation time and more patients are needed to evaluate a beneficial advantage of the CD19/CD22 dual CAR-T over CD19 CAR-T product."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • IFNG • IL10 • IL2RA • IL6

[VIRTUAL] A Feasibility and Safety Study of a Novel CD19-Directed Synthetic T-Cell Receptor and Antigen Receptor (STAR) T-Cell Therapy for Refractory and Relapsed (R/R) B Cell Acute Lymphoblastic Leukemia (B-ALL) (ASH 2020) - P1 | "Here, we report pre-clinical and first-in-human phase I trial results of CD19 STAR-T cell therapy for CD19+ R/R B-ALL...Patients received a conditioning regimen of IV fludarabine (25mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single STAR T-cell infusion...A high CR could be achieved on day 14 with low toxicity. Longer-term observation of these patients and studies of larger patient cohorts are warranted."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD19

[VIRTUAL] Successful 24-Hours Manufacture of Anti-CD19/CD22 Dual Chimeric Antigen Receptor (CAR) T Cell Therapy for B-Cell Acute Lymphoblastic Leukemia (B-ALL) (ASH 2020) - P1 | "All patients received a conditioning regimen of IV fludarabine (25mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days prior to GC022F infusion...Our clinical data demonstrate that GC022F is safe and efficacious in treating patients with CD19+CD22+ B-ALL. More data on additional patients and longer observation time are needed to further evaluate CD19/CD22 dual FasTCAR-T cell product."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CCR7 • LAG3 • PD-1

Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia. (PubMed, Front Immunol) - "Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials."

CAR T-Cell Therapy • Clinical • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD19

Promoter usage regulating the surface density of CAR molecules may modulate the kinetics of CAR-T cells in vivo. (PubMed, Mol Ther Methods Clin Dev) - P1 | "These results represent the first comprehensive study on the promoter-driven modulation of CAR-T cell functionality. These findings encourage further evaluation of the potential of the MND promoter to drive CAR-T cells as a broadly applicable cellular product for anticancer immunotherapy."

CAR T-Cell Therapy • Journal • Preclinical • Hematological Malignancies • Leukemia • Oncology • IFNG

Senl-h19 CAR-T Cell Injection in the Treatment of Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P=N/A; N=15; Recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

Clinical • New trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19 • CD7 • IL10 • IL6

Senl_1904A and Senl_1904B Chimeric Antigen Receptor （CAR） T-Cell in the Treatment of r/ r Acute B Lymphocytic Leukemia (clinicaltrials.gov) - P1; N=20; Active, not recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.; Recruiting ➔ Active, not recruiting; Trial completion date: Jan 2020 ➔ Jan 2022; Trial primary completion date: Sep 2019 ➔ Sep 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19

Adult B-ALL Treated by CART Cell Bridging Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

Clinical • New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukaemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia Using CD7-Specific CAR-T Cells (clinicaltrials.gov) - P=N/A; N=20; Recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.; Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD7

Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia Using CD7-Specific CAR-T Cells (clinicaltrials.gov) - P=N/A; N=20; Not yet recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

New trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD7

Immunotherapy With BCMA CAR-T Cells in Treating Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P=N/A; N=20; Recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.; Trial completion date: Dec 2020 ➔ Dec 2022; Trial primary completion date: Aug 2020 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and Efficacy Study of SL1904B CAR-T Cells for Relapsed or Refractory B-Cell Acute Lymphocyte Leukemia (clinicaltrials.gov) - P=N/A; N=20; Recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

Clinical • New trial • Hematological Malignancies • Leukemia • Oncology • CD19

Safety and Efficacy Study of CD22 CAR-T Cells for Relapsed or Refractory Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P=N/A; N=20; Recruiting; Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

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

[VIRTUAL] CD19-TARGETED CAR-T CELL THERAPY FOR 32 B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL) PATIENTS WHO RELAPSED AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO-HSCT) (EBMT 2020) - P1, P1/2 | "All patients received a conditioning regimen of IV fludarabine (30mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single infusion of CAR-T cells with a median dose of 2 x105 (0.083-10x105) cells/kg... Our study demonstrates that a high CR rate can still be achieved through CAR-T therapy even for those who relapsed after allo-HSCT without increasing CRS or neurotoxicity. A second consolidation allo-HSCT may be considered for those who achieved MRD-negative CR after CAR-T. Receiving CAR-T cells that manufactured from transplant donors may result in a trend towards higher GVHD rate compared to autologous CAR-T cells."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukaemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD19

[VIRTUAL] CD19-TARGETED CAR-T CELL THERAPY FOR 32 B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL) PATIENTS WHO RELAPSED AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO-HSCT) (EBMT 2020) - P1, P1/2 | "All patients received a conditioning regimen of IV fludarabine (30mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single infusion of CAR-T cells with a median dose of 2 x105 (0.083-10x105) cells/kg... Our study demonstrates that a high CR rate can still be achieved through CAR-T therapy even for those who relapsed after allo-HSCT without increasing CRS or neurotoxicity. A second consolidation allo-HSCT may be considered for those who achieved MRD-negative CR after CAR-T. Receiving CAR-T cells that manufactured from transplant donors may result in a trend towards higher GVHD rate compared to autologous CAR-T cells."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukaemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD19

[VIRTUAL] CD19-TARGETED CAR-T CELL THERAPY FOR 32 B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL) PATIENTS WHO RELAPSED AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO-HSCT) (EBMT 2020) - P1, P1/2 | "All patients received a conditioning regimen of IV fludarabine (30mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single infusion of CAR-T cells with a median dose of 2 x105 (0.083-10x105) cells/kg... Our study demonstrates that a high CR rate can still be achieved through CAR-T therapy even for those who relapsed after allo-HSCT without increasing CRS or neurotoxicity. A second consolidation allo-HSCT may be considered for those who achieved MRD-negative CR after CAR-T. Receiving CAR-T cells that manufactured from transplant donors may result in a trend towards higher GVHD rate compared to autologous CAR-T cells."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukaemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD19

[VIRTUAL] CD19-TARGETED CAR-T CELL THERAPY FOR 32 B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL) PATIENTS WHO RELAPSED AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO-HSCT) (EBMT 2020) - P1, P1/2 | "All patients received a conditioning regimen of IV fludarabine (30mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single infusion of CAR-T cells with a median dose of 2 x105 (0.083-10x105) cells/kg... Our study demonstrates that a high CR rate can still be achieved through CAR-T therapy even for those who relapsed after allo-HSCT without increasing CRS or neurotoxicity. A second consolidation allo-HSCT may be considered for those who achieved MRD-negative CR after CAR-T. Receiving CAR-T cells that manufactured from transplant donors may result in a trend towards higher GVHD rate compared to autologous CAR-T cells."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukaemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD19