zamtocabtagene autoleucel (MB-CART2019.1) / Miltenyi Biomedicine - LARVOL DELTA

Cellular Kinetics, Efficacy, and Safety of Zamtocabtagene Autoleucel, a Tandem CD20/CD19-Directed CAR T-Cell Therapy, vs R-GemOx in Patients With Relapsed/Refractory LBCL (DALY 2-EU Study) (SOHO 2026) - " In this randomized, multicenter, open-label phase 3 study, transplant-ineligible adults with R/R LBCL received zamto-cel or rituximab plus gemcitabine and oxaliplatin (RGemOx; ± polatuzumab vedotin). Zamto-cel demonstrated clinically meaningful superiority over R-GemOx in transplant-ineligible patients with R/R LBCL. CAR T-cell expansion correlated with efficacy and toxicity outcomes, supporting the biological relevance of CK parameters in this setting."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Zamtocabtagene Autoleucel, a Tandem CD20-CD19 CAR T-Cell Therapy in Relapsed/Refractory Large B-Cell Lymphoma: Third-Line Crossover Analysis From the Randomized DALY 2-EU Trial (SOHO 2026) - "Context: Patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem cell transplantation have limited treatment options. Patients crossing over to zamto-cel achieved high response rates with manageable toxicity despite more refractory disease. These findings support the use of zamto-cel in both second-line and third-line settings for chemotherapy-refractory LBCL. This is an encore abstract previously presented as a poster at the EHA Annual Meeting 2026."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Interim Results from a Phase 2 Pivotal Study (DALY II USA) of Tandem CD20-CD19-Directed Non-Cryopreserved CAR-T Cells - Zamtocabtagene Autoleucel (Zamto-Cel) in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma (ASH 2024) - P2 | "Lymphodepletion chemotherapy was initiated during the manufacturing process (either cyclophosphamide/ fludarabine or bendamustine) prior to receiving a single dose of zamto-cel at a dose of 2.5x106 CAR T cells/kg on Day 0. Unlike currently registered CAR-T cell products, zamto-cel is administered as a fresh product with a short vein-to-vein time of 14 days with lymphodepletion initiated during the manufacturing process. With a manufacturing success rate of 91% we have demonstrated the feasibility of this process among high-risk patients with r/r DLBCL."

CAR T-Cell Therapy • Clinical • IO biomarker • P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • CD20

TANDEM CD20-19-DIRECTED NON-CRYOPRESERVED CAR-T CELLS–ZAMTOCABTAGENE AUTOLEUCEL (ZAMTO-CEL)—IN PATIENTS WITH RELAPSED/REFRACTORY CNS LYMPHOMA IN DALY II US STUDY (ICML 2025) - P2 | "Lymphodepletion chemotherapy with cyclophosphamide/fludarabine was initiated during the manufacturing process prior to a single infusion of zamto-cel at a dose of 2.5 × 106 CAR-T cells/kg. Zamto-cel exhibited a favorable safety profile and was well tolerated in patients with r/r CNSL with encouraging efficacy in the majority of treated patients. Longer follow-up time is needed to evaluate the duration of response. Dual targeting and the very short vein-to-vein time may be beneficial in this rapidly growing disease."

CAR T-Cell Therapy • Clinical • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma • CD20

Interim Analysis of a Phase II Study of Administered Fresh Bispecific Anti-CD20/Anti-CD19 CAR T-Cell Therapy - Zamtocabtagene Autoleucel (zamto-cel) for Relapsed/Refractory (R/R) DLBCL (DALY II USA NCT04792489) (TCT-ASTCT-CIBMTR 2023) - P2 | "Predetermined interim analysis of zamto-cel showed low toxicity with encouraging efficacy in a DLBCL population that was pre-treated with agents not previously available. This study demonstrates the success of a rapid manufacturing process with 100% fresh infusion in eligible pts."

CAR T-Cell Therapy • P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

BISPECIFIC ANTI-CD20/19 CAR-T—ZAMTOCABTAGENE AUTOLEUCEL FOR RELAPSED/REFRACTORY DLBCL—INTERIM ANALYSIS RESULTS OF DALY-II-USA STUDY (ICML 2023) - "The prespecified efficacy threshold of zamto-cel was exceeded in the interim analysis Treatment demonstrated a favorable safety profile, with promising ORR and PFS in advanced DLBCL population often pre-treated with agents not available in previous similar studies. We also demonstrate the feasibility of a rapid manufacturing process with 100% fresh infusion in eligible pts. Encore Abstract—previously submitted to EHA 2023"

Diffuse Large B Cell Lymphoma • Oncology

INTERIM RESULTS OF TANDEM CD20-CD19-DIRECTED NON-CRYOPRESERVED CAR-T CELLS—ZAMTOCABTAGENE AUTOLEUCEL IN RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA (ICML 2025) - P2 | "This pre-planned interim analysis represents the first pivotal trial of a tandem CD20-CD19 directed non-cryopreserved CAR-T cell product for patients with third-line r/r DLBCL. The results show encouraging activity and a favorable safety profile. Unlike currently registered CAR-T cell products, zamto-cel is a dual-targeting, freshly administered product with lymphodepletion started during manufacturing resulting in a short vein-to-vein time with a high manufacturing success rate."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Zamtocabtagene Autoleucel in Relapsed/refractory B-NHL: 5-year Follow Up of a CD20/19 tandem CAR T Cell Phase 1 Trial. (PubMed, Blood Adv) - P1 | "Based on the promising risk-to-benefit ratio, evaluation of zamto-cel at DL2 is ongoing in pivotal Phase II clinical trials for patients with r/r aggressive B-NHL. This trial was registered at www.clinicaltrials.gov as #NCT03870945."

First-in-human • IO biomarker • Journal • P1 data • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD27 • IL7R

Comparative Efficacy and Safety of Available CD19-Directed Chimeric Antigen Receptor T-Cell Therapies for Treatment of Relapsed/Refractory Large B-Cell Lymphomas: A Network Meta-Analysis (SOHO 2026) - " Four databases were searched for studies evaluating four major CAR-T products: axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), and zamtocabtagene autoleucel (zamto-cel)...P-score ranking identified axi-cel as the best overall therapy for OS (P score, 0.93) and PFS (P score, 0.83), whereas lisocel ranked highest for EFS (P score, 0.82)... Among currently available CAR-T therapies, axi-cel appears to demonstrate the strongest efficacy profile, with improved response rates and survival outcomes, followed by liso-cel and potentially zamto-cel. Tisa-cel, while ranking lower in efficacy outcomes, appears to be associated with a more favorable safety profile, particularly with regard to neurological toxicities. CAR-T: chimeric antigen receptor T-cell, CD: cluster of differentiation, CI: confidence interval, CRS: cytokine release syndrome, EFS: event-free survival, HR: hazard ratio, NE: neurological events, NHL: non-Hodgkin..."

CAR T-Cell Therapy • Retrospective data • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Lentiviral Gene Therapy (Zamtocabtagene Autoleucel) LTFU (clinicaltrials.gov) - P=N/A | N=150 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial completion date: Dec 2039 ➔ Dec 2041 | Trial primary completion date: Dec 2039 ➔ Dec 2041

Trial completion date • Trial primary completion date • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Gene Therapies • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma

ZAMTOCABTAGENE AUTOLEUCEL, A TANDEM CD20-CD19 DIRECTED CAR-T CELL THERAPY IN RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA: CROSSOVER ANALYSIS (THIRD-LINE) FROM THE RANDOMIZED, PIVOTAL DALY 2-EU TRIAL (EHA 2026) - P2 | "Zamto-cel pts started lymphodepletion (fludarabine and cyclophosphamide) during manufacturing and received zamto-cel (target dose of 2.5×10 6 CAR-T cells/kg body weight). Summary/Conclusion In this 3L setting, most intended pts received zamto-cel. Analysis of this mainly refractory 3L pt population revealed clinically meaningful efficacy of zamto-cel with low rates of severe CRS and ICANS, consistent with second-line treatment with zamto-cel."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pulmonary Disease • Respiratory Diseases • Septic Shock • CD20

M-2024-423: US Zamto-cel Autoimmune Diseases (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2026 ➔ Jul 2028 | Trial primary completion date: Dec 2026 ➔ Jan 2028

Enrollment open • Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART2019.1 in Refractory Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=26 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2030 ➔ Aug 2030 | Trial primary completion date: Feb 2030 ➔ Aug 2030

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

DALY 2-EU: Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients (clinicaltrials.gov) - P2 | N=213 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Active, not recruiting ➔ Recruiting | N=45 ➔ 213

Enrollment change • Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

FRONTIER: Frontline Risk-Adapted Optimization of Novel Targeted Immunotherapy Evaluation in High-Risk MCL (clinicaltrials.gov) - P2 | N=52 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH

New P2 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CCND1 • TP53

Zamtocabtagene autoleucel: dual CD20-CD19 targeting for NHL. (PubMed, Blood Adv) - No abstract available

Journal

M-2024-424: MB-CART2019.1 in refractory MS (clinicaltrialsregister.eu) - P1/2 | N=25 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Multiple Sclerosis

Cellular Kinetics, Efficacy, and Safety of Zamtocabtagene Autoleucel, a Tandem CD20-CD19 Directed CAR-T Cell Therapy, vs R-GemOx in Patients with Relapsed/Refractory LBCL (DALY 2-EU Study) (EHA-EBMT-CART 2026) - P2 | "We report cellular kinetic (CK) analyses, in context of efficacy and safety, of the pivotal, DALY 2-EU trial (NCT04844866), comparing zamto-cel and rituximab-gemcitabine-oxaliplatin (R-GemOx) as second-line therapy for relapsed/refractory (r/r) large B-cell lymphoma (LBCL) in transplant-ineligible patients. Clinical Trial Registry : ClinicalTrials.gov: Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients (DALY 2-EU). https://clinicaltrials.gov/study/NCT04844866."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • CD20

Zamtocabtagene Autoleucel (Zamto-Cel), a Tandem CD20-CD19 Directed CAR-T cell Therapy As Second-Line Treatment for relapsed/refractory Large B-cell Lymphoma: Primary analysis of the Randomized, Pivotal DALY 2-EU Study (TCT-ASTCT-CIBMTR 2026) - P2 | "Pts in the zamto-cel arm started lymphodepletion fludarabine + cyclophosphamide during manufacturing, followed by infusion of zamto-cel, target dose 2.5 × 10 6 CAR-T cells/kg body weight...For CRS, 29 38% pts received tocilizumab, 14 18% corticosteroids...4 . To understand the potential mechanistic advantages of a dual-targeting CD20/CD19 CAR-T construct in the treatment of r/r LBCL, as investigated in the DALY 2-EU trial"

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • CD20

DALY II Japan/MB-CART2019.1 for DLBCL (clinicaltrials.gov) - P2 | N=31 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • BCL2 • BCL6 • CD20

DALY 2-EU: Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | N=168 ➔ 45 | Trial completion date: Jul 2029 ➔ Sep 2031

Enrollment change • Trial completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD19

Mapping the immune orchestra of zamtocabtagene autoleucel in primary CNS lymphoma. (PubMed, Haematologica) - "Not available."

Journal • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

DALY II Japan/MB-CART2019.1 for DLBCL (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH

New P2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Zamtocabtagene autoleucel, a tandem CD20-CD19 directed CAR-T cell therapy as second-line treatment for Relapsed/Refractory large B-cell lymphoma: primary analysis of the randomized, pivotal DALY 2-EU study. (ASH 2025) - P2 | "Key inclusion criteria were LBCL, ECOG PS ≤ 2, age ≥ 18 years (y) and one NTE criterion,age ≥ 65 y and impaired organ function or age ≥70 y. Pts in the zamto-cel arm started lymphodepletion(fludarabine and cyclophosphamide) during manufacturing, followed by infusion of a non-cryopreservedzamto-cel product, target dose 2.5 × 106 CAR-T cells/kg body weight...For CRS 29 (38%) pts received tocilizumab and 14 (18%) corticosteroids... Zamto-cel demonstrated highly significant and clinically meaningful superiority over R-GemOx in NTE patients at high risk for treatment failure. Moreover, zamto-cel was well tolerated in thisvulnerable elderly patient population with low rates of severe CRS and ICANS. This favorable risk/benefitprofile suggests the use of zamto-cel as preferred treatment option in 2L for NTE patients with r/r LBCL."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • CD20

MB-CART2019.1 in Refractory Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=26 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH | Initiation date: Oct 2025 ➔ Jan 2026

Trial initiation date • CNS Disorders • Multiple Sclerosis