anti-CD33 CAR T / City of Hope, National Cancer Institute - LARVOL DELTA

A CD33-DELETED ALLOGRAFT (TREM-CEL) ENABLES GEMTUZUMAB OZOGAMICIN MAINTENANCE POST-HEMATOPOIETIC CELL TRANSPLANT WITH THERAPEUTIC EXPOSURES AND LOW TOXICITY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (EHA 2025) - P1/2 | "Aims: Tremtelectogene empogeditemcel (trem-cel, formerly VOR33) is a hematopoietic stem and progenitor cell product produced by CRISPR/Cas9 gene-editing to delete CD33 from CD34+ cells allowing CD33-directed targeting of leukemia while sparing the donor graft...Donor CD34+ cells are isolated from G-CSF/plerixafor-mobilized peripheral blood...If patients relapse post-HCT, they may receive a fractionated induction dose of GO and/or are eligible to receive donor-derived CD33 CAR-T on the VBP301 trial (NCT05984199).25 patients received trem-cel with a median dose of 8.11x106 CD34+ cells/kg (2.62-12.44) and CD33 editing efficiency median 90% (71-94%)... Preliminary results from VBP101 show trem-cel rapidly engrafts, sustains hematopoiesis with persistent myeloid absence of CD33 and protects from prolonged deep GO-associated cytopenias. GO exposures correlate with higher doses seen in R/R AML patients, likely due to reduction CD33-mediated clearance and supports an..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CD33 • CD34

CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Sep 2026 ➔ Sep 2028 | Trial primary completion date: Sep 2026 ➔ Sep 2028

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33

Autologous CD33CART for Children and Adolescents/Young Adults with Relapsed/Refractory AML: Phase 1/2 Clinical Trial Correlative Biology Analyses Demonstrate Potent in Vitro, In Vivo, and Ex Vivo Anti-Leukemia Activity (ASH 2024) - P1/2 | "PDX modeling demonstrated successful engraftment of 7 of 14 (50%) rrAML patient specimens in busulfan-conditioned immunocompromised mice. Additional laboratory studies to elucidate potentially deleterious T cell- or AML-intrinsic and microenvironmental factors are in process. The trial is now accruing in an allogeneic arm using hematopoietic stem cell transplant donor-derived T cells."

IO biomarker • P1/2 data • Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CCL4 • CD22 • CD4 • CD8 • GZMB • IFNG • IL2 • IL5 • TGFB1 • TNFA

Success of Centralized Manufacturing of CD33 CAR T-Cells (CD33CART) for Children and Young Adults with Relapsed/Refractory AML (TCT-ASTCT-CIBMTR 2024) - P1/2 | "Despite wide inter-patient heterogeneity of apheresis products, centralized manufacturing of CD33CART was feasible in children and young adults with r/r AML. Correlative analyses characterizing CD33CART products are ongoing."

CAR T-Cell Therapy • Clinical • Acute Myelogenous Leukemia • CD4 • CD8 • IL2

CD33 CAR T-Cells (CD33CART) for Children and Young Adults with Relapsed/Refractory AML: Dose-Escalation Results from a Phase I/II Multicenter Trial (ASH 2023) - P1/2 | "All subjects received pre-CD33CART lymphodepleting chemotherapy (LD) with fludarabine (75-120 mg/m2) and cyclophosphamide (900-1000 mg/m2). CD33CART manufacturing is feasible in children and AYAs with r/r AML with acceptable toxicity experienced in treated subjects. CD33CART expansion was best in subjects treated at DL4 (1 x 107/kg) with MRD negative CRs and transient myeloid aplasia occurring in 2 of 5 (40%) subjects evaluable for response (Table). Based on early clinical efficacy at DL4, enrollment continues in the phase 2 portion."

CAR T-Cell Therapy • Clinical • P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Obesity • Palliative care • Pediatrics • Transplantation

CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Nov 2025 ➔ Sep 2026 | Trial primary completion date: Nov 2025 ➔ Sep 2026

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33

CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Initiation date: May 2023 ➔ Aug 2023

CAR T-Cell Therapy • Enrollment open • Trial initiation date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33

Combining Anti-CD33 Chimeric Antigen-Receptor T Cells with the Hypomethylating Agent Decitabine to Treat Acute Myeloid Leukemia (ASGCT 2023) - "Acute myeloid leukemia (AML) is the most common acute leukemia in adults, causing >10,000 deaths per year in the United States. Moreover, DAC treatment resulted in downregulation of DNA repair pathways, β-Catenin, and Notch signaling pathways.Taken together, we found that the antileukemia activity of CD33 CAR T cells was enhanced by pretreatment of leukemia cells with DAC. This combination represents a clinically relevant therapy for the treatment of patients with r/r AML."

CAR T-Cell Therapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Leukemia • Oncology • CD33 • CD4 • CD8 • DNMT1 • DNMT3A • DNMT3B

CD33 CAR T Cells Generated by Restrained TCR Stimulation and Optimized Cytokines Manifested Potent Antileukemic Activity and Less-Differentiated Memory Phenotype (ASGCT 2023) - "Our previous clinical trial of CD123 CAR T cells was promising but identified the need for a faster CAR T cell manufacturing process. Using a combination of restrained TCR stimulation (4D-2:1 bead) and IL2/IL15 cytokines, we optimized our CD33 CAR T cell production platform to yield highly proliferative CAR T cells with less-differentiated memory phenotype and potent antigen-dependent antileukemic efficacy."

CAR T-Cell Therapy • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD123 • CD33 • CD8 • IL15 • IL2 • IL7

CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: City of Hope Medical Center

CAR T-Cell Therapy • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33