CAR20.19.22 T / Miltenyi Biotec, Medical College of Wisconsin - LARVOL DELTA

Phase 1 Study of Trispecific Anti-CD20, Anti-CD19, Anti-CD22 (CAR20.19.22) T Cells for Relapsed, Refractory B-Cell Malignancies (ASH 2024) - P1 | "Standard fludarabine/cyclophosphamide lymphodepletion was administered prior to infusion...In terms of safety, two patients had Grade 1 CRS and received tocilizumab for management...From a product characteristic standpoint, CAR20.19.22 T cells had similar cytotoxicity, CD4 : CD8 ratios, CD3 T-cell expansion during manufacture, and transduction efficiency as patients treated with LV20.19 CAR T cells on a prior clinical trial...While preclinical xenograft studies for this vector demonstrated potent in-vivo efficacy, these data demonstrate the importance of human investigation and how manipulations in CAR design can impact construct efficacy. To our knowledge this is the first ICOS CAR administered to humans, and these early findings suggest careful consideration is needed for future CARs dependent on ICOS signaling rather than traditional 41BB or CD28 co-stimulation."

IO biomarker • P1 data • Trispecific • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • CD8 • ICOS

CAR20.19.22 T-cells in Relapsed, Refractory B-cell Malignancies (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Medical College of Wisconsin | All four patients had no in-vivo expansion and no meaningful response to therapy. At this point per FDA guidance we will not be treating more patients.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

CAR20.19.22 T-cells in Relapsed, Refractory B-cell Malignancies (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Medical College of Wisconsin | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

CAR20.19.22 T-cells in Relapsed, Refractory B-cell Malignancies (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Medical College of Wisconsin | N=36 ➔ 48

Enrollment change • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2