TAK-940 / Takeda, Memorial Sloan-Kettering Cancer Center - LARVOL DELTA

Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma (J Clin Oncol) - P1 | N=30 | NCT04464200 | "Twenty-eight patients underwent apheresis and received CAR T cells. Sixteen and 12 patients were treated in the dose escalation and expansion cohorts, respectively. The overall response rate (ORR) was 82% and complete response (CR) rate was 71% in the entire cohort. The lowest dose of 25 × 106 was selected for dose expansion. In 16 patients treated at this DL, 88% achieved ORR and 75% CR. With the median follow-up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond 12 months. In all cohorts, grade ≥3 cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome rates were low at 4% and 7%, respectively."

P1 data • Large B Cell Lymphoma

Takeda drops cancer candidates, axing immunocytokine and CAR-Ts amid shifting treatment landscape (Fierce Pharma) - "Takeda’s vision of becoming a leader in oncology ran into more trouble Thursday when the drugmaker axed (PDF) a midphase immunocytokine and three early-stage CAR-T cell therapy prospects from its R&D pipeline...Takeda pushed modakafusp alfa out of the door as part of a pipeline clear-out that also hit three phase 1 autologous CAR-T candidates. Two of the prospects, GPC3-targeted TAK-102 and mesothelin-directed TAK-103, were in development in solid tumors. The third asset, TAK-940, was a CD19-directed, Memorial Sloan Kettering Cancer Center-partnered program that used the 1XX domain to try to enhance efficacy....While Takeda axed a clutch of cancer candidates, Plump said the company 'remains committed to oncology and will continue to develop therapies across hematologic and solid tumors.'"

Discontinued • Hematological Malignancies • Oncology • Solid Tumor

Role of Cell Therapy Product Characteristics in Patient Response to TAK-940 (CD19(T2)28z1xx Chimeric Antigen Receptor (CAR) T): Biomarker Analyses from a Phase I Study in Adult Patients with Relapsed or Refractory B-Cell Malignancies (ASH 2023) - P1 | "Increase in CD57+ CAR+ T cell subsets has been previously associated with durable CRs in large B cell lymphoma patients treated with axi-cel (Good Z et al. Correlative analysis of T cell immunophenotypes observed in the product to clinical parameters including durability of responses, metabolic tumor volume/tumor burden, and induction of cytokines and chemokines is ongoing and will be reported. This will further contribute to our understanding of CD19 CAR T cells endowed with a 1XX signaling domain and potentially support the identification of product and/or apheresis biomarkers that may predict patient response."

Biomarker • Clinical • IO biomarker • P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B3GAT1 • CD4 • CD8 • HAVCR2 • IFNG • IL10 • IL6 • KLRG1 • LAG3

Takeda Opens New R&D Cell Therapy Manufacturing Facility to Support Expansion of Next-Generation Clinical Programs (Takeda Press Release) - "Takeda Pharmaceutical Company Limited...announced the expansion of its cell therapy manufacturing capabilities with the opening of a new 24,000 square-foot R&D cell therapy manufacturing facility at its R&D headquarters in Boston...Takeda and MD Anderson are developing a potential best-in-class allogeneic cell therapy product (TAK-007), a Phase 1/2 CD19-targeted chimeric antigen receptor-directed natural killer (CAR-NK) cell therapy with potential for off-the-shelf use being studied in patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Two additional Phase 1 studies of Takeda cell therapy programs were also recently initiated: 19(T2)28z1xx CAR T cells (TAK-940)...to treat relapsed/refractory B-cell cancers, and a cytokine and chemokine armored CAR-T (TAK-102)....to treat GPC3-expressing previously treated solid tumors."

Clinical • Trial status • Chronic Lymphocytic Leukemia • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Memorial Sloan Kettering Cancer Center

Clinical • New P1 trial • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology