CAR T-cell therapeutics / MabVax, Memorial Sloan-Kettering Cancer Center - LARVOL DELTA

KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: END OF PHASE 1 RESULTS OF ZUMA-3 (EHA 2019) - P1/2; "Background KTE-X19 is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy under investigation for adult relapsed/refractory acute lymphoblastic leukemia. Conclusion KTE-X19 dosing and safety management have been successfully refined by testing 3 cell doses and evaluating a new AE management guideline with altered corticosteroids/tocilizumab use for NEs/CRS. The pivotal Phase 2 portion of ZUMA-3 is ongoing at the 1 × 106 dose with revised AE management."

CAR T-Cell Therapy • Clinical • P1 data

DURABLE LONG-TERM SURVIVAL OF ADULT PATIENTS WITH B-ALL AFTER CD19 CAR (19-28Z) T CELL THERAPY (EHA 2017) - P1; "Despite comparable initial CR rates regardless of pre-treatment disease burden, durability of 19-28z CAR T cell mediated remissions and survival in adult patients with relapsed B-ALL positively correlated to a low disease burden and do not appear to be enhanced by allogeneic transplant. Our findings strongly support the early incorporation of CD19 CAR therapy before morphologic relapse in B-ALL."

CAR T-Cell Therapy • Clinical

BASELINE AND EARLY POST-TREATMENT CLINICAL AND LABORATORY FACTORS ASSOCIATED WITH SEVERE NEUROTOXICITY FOLLOWING 19-28Z CAR T CELLS IN ADULT PATIENTS WITH RELAPSED B-ALL (EHA 2017) - P1; "These data provide a characterization of early clinical and serum biomarkers of sNTX in adult pts receiving 19-28z CAR T cells and should help identify appropriate pts for early intervention strategy to mitigate NTX."

CAR T-Cell Therapy

Impact and Safety of Chimeric Antigen Receptor T Cell Therapy in Vulnerable Older Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (ASH 2019) - "We retrospectively examined outcomes of older patients referred for commercial CAR T products, axicabtagene ciloleucel and tisagenlecleucel, at our institution from January 2018 to March 2019. Detailed geriatric assessment and correlation with toxicities should allow better selection of older adults who could benefit from this curative treatment. In addition, the biology of CAR T response in older adults may warrant additional investigation in the context of aging-associated changes in the immune system."

CAR T-Cell Therapy • Clinical

Sequential Anti-CD19 Directed Chimeric Antigen Receptor Modified T-Cell Therapy (CART19) and PD-1 Blockade with Pembrolizumab in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas (ASH 2018) - P1/2, P2, P2a; "Introduction : Chimeric antigen receptor modified T cells directed against CD19 (CART19) achieve durable remissions in about 30-40% of relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL); this led to recent FDA approvals of tisagenlecleucel (Schuster NEJM 2017, Schuster ASH 2017) and axicabtagene ciloleucel (Neelapu NEJM 2017). Analysis of the pharmacokinetics of CAR T-cells in pts treated with pembrolizumab appears to identify responding pts and supports the hypothesis that, in some pts, CAR T cells expand following PD1 blockade. Additional studies examining the immunophenotype of CAR T cells in detail are in progress and will be presented."

Clinical • Biosimilar • Cytomegalovirus Infection • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Indolent Lymphoma • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] Preliminary Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Subcutaneously (SC) Administered PF-06863135, a B-Cell Maturation Antigen (BCMA)-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2020) - P1 | "The median number of prior anticancer treatment regimens was 7; all patients had received prior daratumumab therapy; 4 (22%) patients had received prior BCMA-targeted antibody–drug conjugate or chimeric antigen receptor T-cell therapy. Clinicaltrials.gov identifier: NCT03269136. Funding: Pfizer."

Clinical • IO biomarker • PK/PD data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Septic Shock • Thrombocytopenia • CD38

CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T-cell product JCAR017 (TRANSCEND NHL 001). (ASCO 2017) - P1; "...No severe cytokine release syndrome (sCRS) was observed; 10 patients had grade 1-2 CRS (1 received tocilizumab)... Treatment with JCAR017 results in high CR rate in patients with heavily pretreated R/R DLBCL. Relapses can occur despite persistence of JCAR017, suggesting tumor immune evasion mechanisms may contribute to relapse. Observed toxicities are manageable and occurred at rates lower than those reported for other CD19-directed CAR T cell products."

Biomarker • CAR T-Cell Therapy • Clinical • Biosimilar • Diffuse Large B Cell Lymphoma

Durable long-term survival of adult patients with relapsed B-ALL after CD19 CAR (19-28z) T-cell therapy. (ASCO 2017) - P1; "Despite comparable initial CR rates regardless of pre-treatment disease burden, durability of 19-28z CAR T cell mediated remissions and survival in adult patients with relapsed B-ALL positively correlated to a low disease burden and do not appear to be enhanced by allogeneic transplant. Our findings strongly support the early incorporation of CD19 CAR therapy before morphologic relapse in B-ALL."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Biosimilar

Baseline and early post-treatment clinical and laboratory factors associated with severe neurotoxicity following 19-28z CAR T cells in adult patients with relapsed B-ALL. (ASCO 2017) - P1; "These data provide a characterization of early clinical and serum biomarkers of sNTX in adult pts receiving 19-28z CAR T cells and should help identify appropriate pts for early intervention strategy to mitigate NTX."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • Biosimilar

Biomarkers associated with neurotoxicity in adult patients with relapsed or refractory B-ALL (R/R B-ALL) treated with CD19 CAR T cells. (ASCO 2017) - P1; "NTX is predominantly reversible. MRI findings suggesting transient toxicity to deep grey structures and findings of a CSF-specific cytokine profile expand the hypotheses on the mechanism of NTX. Future studies will focus on determining the etiology of the CSF protein elevation and the distinct cytokine profile."

Biomarker • CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Biosimilar • Epilepsy

[VIRTUAL] CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen–Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory Multiple Myeloma (ASH 2020) - P1b | "Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 d were used for lymphodepletion. Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated pts with MM with a safety profile consistent with LEGEND-2. Further investigation of cilta-cel in other MM populations is underway."

CAR T-Cell Therapy • IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Leukemia • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • Transplantation • CD38

UPDATED SAFETY & LONG TERM CLINICAL OUTCOMES IN TRANSCEND NHL 001, PIVOTAL TRIAL OF LISOCABTAGENE MARALEUCEL (JCAR017) IN R/R AGGRESSIVE NHL (EHA 2018) - P1; "Background: Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in defined composition at a precise dose of CD8 and CD4 CAR T cells...Treatment includes lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel...Nineteen pts (21%) received tocilizumab and/or dexamethasone... Liso-cel shows durable responses in pts with heavily pretreated R/R DLBCL and trends toward more durable responses at DL2. Observed acute toxicities have been manageable at all DLs tested and long-term safety from the initial cohort will be reported."

Clinical • Diffuse Large B Cell Lymphoma • Follicular Lymphoma

AG-636 for the Treatment of Adults with Advanced Lymphoma: Initiation of a Phase 1 Clinical Study (ASH 2019) - P1; "Inhibitors of DHODH are currently in clinical use for the treatment of rheumatoid arthritis (leflunomide) and multiple sclerosis (teriflunomide)...There are no limits on the number of prior lines of therapy and patients may have received prior stem cell transplant or chimeric antigen receptor T-cell therapy...Further expansion may be undertaken if AG-636 shows high activity in specific subtypes of lymphoma, either in the clinic or in preclinical models. The experience in this study with the pharmacokinetics, pharmacodynamics, and safety of AG-636 will inform the optimal starting dose and regimen for evaluation in subsequent studies."

Clinical • New P1 trial • P1 data • CNS Disorders • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Leukemia • Lymphoma • Multiple Sclerosis • Oncology • Rheumatoid Arthritis • Rheumatology

[VIRTUAL] Subcutaneous Mosunetuzumab in Relapsed or Refractory B-Cell Lymphoma: Promising Safety and Encouraging Efficacy in Dose Escalation Cohorts (ASH 2020) - P1 | "Median prior systemic therapies was 4 (range: 1–8); five pts (22%) had received prior chimeric antigen receptor T-cell therapy...In SC pts, CRS events resolved without tocilizumab treatment, intensive care unit admission or use of vasopressors...These results support continued dose escalation and optimization of Mosun SC in R/R B-NHL. Updated clinical, PK and biomarker data, including approximately 20 additional pts from an interim expansion cohort, will be presented."

Clinical • IO biomarker • CNS Disorders • Critical care • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Mental Retardation • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Otorhinolaryngology • Pain • Psychiatry • IL6

[VIRTUAL] CARTITUDE-1: PHASE 1B/2 STUDY OF CILTACABTAGENE AUTOLEUCEL, A B-CELL MATURATION ANTIGEN–DIRECTED CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (EBMT 2021) - P1b | "Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days were used for lymphodepletion.  Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated patients with MM with a safety profile consistent with LEGEND-2. Cilta-cel is under further investigation in other MM populations. Clinical Trial Registry: NCT03548207 https://www.clinicaltrials.gov/ct2/show/NCT03548207?term=NCT03548207&draw=2&rank=1"

CAR T-Cell Therapy • P1/2 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation

[VIRTUAL] CARTITUDE-1: PHASE 1B/2 STUDY OF CILTACABTAGENE AUTOLEUCEL, A B-CELL MATURATION ANTIGEN–DIRECTED CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (EBMT 2021) - P1b | "Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days were used for lymphodepletion.  Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated patients with MM with a safety profile consistent with LEGEND-2. Cilta-cel is under further investigation in other MM populations. Clinical Trial Registry: NCT03548207 https://www.clinicaltrials.gov/ct2/show/NCT03548207?term=NCT03548207&draw=2&rank=1"

CAR T-Cell Therapy • P1/2 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation

[VIRTUAL] CARTITUDE-1: PHASE 1B/2 STUDY OF CILTACABTAGENE AUTOLEUCEL, A B-CELL MATURATION ANTIGEN–DIRECTED CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (EBMT 2021) - P1b | "Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days were used for lymphodepletion.  Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated patients with MM with a safety profile consistent with LEGEND-2. Cilta-cel is under further investigation in other MM populations. Clinical Trial Registry: NCT03548207 https://www.clinicaltrials.gov/ct2/show/NCT03548207?term=NCT03548207&draw=2&rank=1"

CAR T-Cell Therapy • P1/2 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation

[VIRTUAL] CARTITUDE-1: PHASE 1B/2 STUDY OF CILTACABTAGENE AUTOLEUCEL, A B-CELL MATURATION ANTIGEN–DIRECTED CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (EBMT 2021) - P1b | "Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days were used for lymphodepletion.  Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated patients with MM with a safety profile consistent with LEGEND-2. Cilta-cel is under further investigation in other MM populations. Clinical Trial Registry: NCT03548207 https://www.clinicaltrials.gov/ct2/show/NCT03548207?term=NCT03548207&draw=2&rank=1"

CAR T-Cell Therapy • P1/2 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation

[VIRTUAL] High Rates of Residual Vaccine Titers at 1-Year Post CD19 Chimeric Antigen Receptor T Cell Therapy (TCT-ASTCT-CIBMTR 2021) - "Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19. Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Tetanus • Transplantation • Varicella Zoster • CD19 • CD8

[VIRTUAL] High Rates of Residual Vaccine Titers at 1-Year Post CD19 Chimeric Antigen Receptor T Cell Therapy (TCT-ASTCT-CIBMTR 2021) - "Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19. Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Tetanus • Transplantation • Varicella Zoster • CD19 • CD8

[VIRTUAL] High Rates of Residual Vaccine Titers at 1-Year Post CD19 Chimeric Antigen Receptor T Cell Therapy (TCT-ASTCT-CIBMTR 2021) - "Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19. Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Tetanus • Transplantation • Varicella Zoster • CD19 • CD8

[VIRTUAL] High Rates of Residual Vaccine Titers at 1-Year Post CD19 Chimeric Antigen Receptor T Cell Therapy (TCT-ASTCT-CIBMTR 2021) - "Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19. Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Tetanus • Transplantation • Varicella Zoster • CD19 • CD8

[VIRTUAL] High Rates of Residual Vaccine Titers at 1-Year Post CD19 Chimeric Antigen Receptor T Cell Therapy (TCT-ASTCT-CIBMTR 2021) - "Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19. Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Tetanus • Transplantation • Varicella Zoster • CD19 • CD8

[VIRTUAL] Clinical Impact of Bridging Therapy Prior to Commercial Chimeric Antigen Receptor (CAR) T-Cell Therapies for Relapsed/Refractory Lymphomas (ASH 2020) - "Background: CD19-targeted chimeric antigen receptor T-cell therapies (CART) have remarkable overall response rates (ORR) for relapsed/refractory diffuse large B cell lymphoma (DLBCL)...Pts received axicabtagene ciloleucel (axi-cel, 68%) or tisagenlecleucel (tisa-cel, 32%) following lymphodepletion (LD) with median Aph to infusion time of 35d (range 20–77)...Tocilizumab and steroid use rates were 45% and 41%, respectively and did not differ by BI (p=0.2, p=0.8)...Early data suggest that RT or CMT may be a preferable BI strategy compared to ST though larger cohorts are needed for validation and to clarify the unique impact of RT without ST. More intensive cytoreductive strategies might be beneficial for bulky disease pre-CART."

Clinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD19

Infectious Complications in Aggressive B Cell Non-Hodgkin Lymphoma after CD-19 Chimeric Antigen Receptor T Cell Therapy (TCT-ASTCT-CIBMTR 2020) - " We analyzed 60 consecutive patients with aggressive B cell NHL who received FDA-approved commercial CD19 targeted CAR T cell products (axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel)) at our center between January 2018 and June 2019. Infection is a common and potentially serious complication in B-NHL patients treated with CD19 CAR T cells and can occur late after treatment. Prospective studies of infection prophylactic strategies and correlative immune reconstitution are warranted to provide an insight on appropriate post-CAR T cell therapy infection surveillance."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology