JNJ-67571244 / J&J - LARVOL DELTA

CD33-Deleted Hematopoietic Cells (Trem-Cel) Are Protected from CD33xCD3 Bispecific Antibody Treatment and Produce Significantly Reduced Levels of Inflammatory Cytokines in Preclinical Studies (ASH 2023) - P1/2 | "Taken together, these studies demonstrate that CD33 deleted hematopoietic compartment is protected from the CD33 directed immuno-therapy JNJ-67571244 both in in vitro cytotoxicity assays and preclinical xenotransplantation studies, with decreased concentrations of inflammatory cytokines associated with CRS. These findings enable the development of a next-generation AML treatment strategy by pairing trem-cel transplant with a subsequent CD33-directed bispecific compound to potentially improve safety and efficacy while minimizing myelotoxicity."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ANXA5 • CD14 • CD33 • CD34 • CD69 • IFNG • IL10 • IL2 • IL2RA • IL6 • TNFA

CSF1R Targeting T Cell Engaging Bispecific Antibodies Enable Safe and Efficient Immunotherapies in Acute Myeloid Leukemia (ASH 2024) - "While the use of T cell engaging bispecific antibodies (TCE) targeting B cell lineage antigens such as CD19 (Blinatumomab) or CD20 (Epcoritamab, Glofitamab, Mosuenetuzumab) have induced strong and long-lasting response rates in B cell malignancies (Falchi, Vardhana et al...Early clinical trials of CD33-TCE (JNJ-67571244, AMG330) or CD123-TCE (Vibecotamab) have shown modest clinical activity (response rates ranging between 0 to 16,6%) and a high degree of treatment-emergent adverse events (TEAE) (Ravandi, Bashey et al...In summary, we could show the safety and efficacy of CSF1R-TCB in preclinical in vitro and in vivo models and demonstrate the superior safety profile of CSF1R-TCB compared to CD33-TCB in CB-humanized mouse models. In cell line-derived xenograft models of AML, CSF1R-TCB induced anti-leukemia activity, warranting further preclinical and clinical investigations."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CCL3 • CD123 • CD20 • CD33 • CD34 • CSF1R • CSF2 • IL2 • IL3RA • IL6

CSF1R Targeting T Cell Engaging Bispecific Antibodies Enable Safe and Efficient Immunotherapies in preclinical models of Acute Myeloid Leukemia (DGHO 2025) - "Early trials of CD33-TCEs (JNJ-67571244, AMG330) and CD123-TCEs (Vibecotamab) demonstrated modest activity (0–16.6% response rates) and frequent treatment-emergent adverse events...Whether CSF1R can be effectively targeted by TCEs remained unclear.We developed a CSF1R-targeted TCE (CSF1R-TCE) using CrossMAb® 2+1 TCE format (as used in FDA and EMA-approved Glofitamab) and demonstrated efficacy in vitro and in vivo...Importantly, utilizing a CD34+ cord blood (CB) stem cell-humanized mouse model, CSF1R-TCE led to lower cytokine release and minimal reduction in HSPC counts compared to CD33-TCE (p < 0.01 for GMCSF, MIP1a; p < 0.05 for IL2, IL6, MCP1 and MIP1b detected in serum 24 hours after therapy). In xenograft models using luciferase-labeled Mv4-11 cells, CSF1R-TCE with T cells reduced tumor growth vs. control TCE (p < 0.0001 by day 38).In summary, we could show the safety and efficacy of CSF1R-TCE in preclinical in vitro and in vivo models and demonstrate..."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CCL3 • CD123 • CD33 • CD34 • CSF1R • CSF2 • IL2 • IL3RA • IL6

CSF1R-targeting T cell engaging bispecific antibodies for Acute Myeloid Leukemia treatment (ITOC 2025) - "Background The potential of T-cell engaging bispecific antibodies (TCEs) is illustrated by the success of targeting CD19 (Blinatumomab) and CD20 (Epcoritamab, Glofitamab, Mosuenetuzumab) in relapsed and refractory B-cell non-Hodgkin lymphoma. However, in AML, TCEs targeting CD33 (JNJ-67571244, AMG330) and CD123 (Vibecotamab) have shown low efficacy and high toxicity...Consistent with our single-cell RNA sequencing-based target analysis, the CSF1R-TCE exhibited a superior safety profile than the CD33-TCE while maintaining anti-tumor activity. CSF1R-targeting TCEs may represent a novel immunotherapeutic approach for AML with high translative potential."

Acute Myelogenous Leukemia • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD123 • CD33 • CD34 • CSF1R • IL3RA

First-in-human study of JNJ-67571244, a CD33 × CD3 bispecific antibody, in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome. (PubMed, Clin Transl Sci) - "T-cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ-67571244 efficacy was not achieved, thus MTD and RP2D were not determined."

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Oncology • CD33

[VIRTUAL] JNJ-67571244: A novel anti-CD33 C2 domain binding bispecific antibody with potent T cell redirection activity (AACR-II 2020) - P1 | "Interestingly, several CD33-antibody-based therapies, including gemtuzumab ozogamicin (GO), the only approved anti-CD33 antibody drug conjugate for AML, bind and recognize the V domain of CD33. Lastly, JNJ-67571244 mediated efficient cytotoxicity of cell lines and primary samples regardless of their genotype status (SNP rs12459419 CC, CT and TT), suggesting a potential therapeutic advantage over competitor V-binding antibodies. JNJ-67571244 is currently in Phase 1 clinical trials to treat relapsed/refractory AML and high risk myelodysplastic syndrome (MDS) patients (NCT03915379)."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

An asymmetrical CLL1/CD3 bispecific antibody, ABL602, exhibits CLL1 binding-dependent CD3 binding/activation and antitumor activity in acute myeloid leukemia (AML) mouse model and leukemia blasts from AML patients (ESMO 2022) - "ABL602 induced superior tumor cell killing than 1+1 reference antibody JNJ-67571244. In AML patient blasts, CLL1 was highly expressed and ABL602 exhibited a strong T cell activation and tumor killing activity on CLL1 + AML blasts. Conclusions This study supports the target-specific T cell activation and tumor killing activity of 2+1 heterodimeric structure of ABL602 on both AML cell lines and patient-originated AML blasts and warrants further pre-clinical development."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • CD33

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=68 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed | Trial completion date: Oct 2022 ➔ Mar 2022

Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • IL10 • IL2RA • IL6

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=68; Active, not recruiting; Sponsor: Janssen Research & Development, LLC; Recruiting ➔ Active, not recruiting; N=180 ➔ 68

Clinical • Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • IL10 • IL2RA • IL6

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=180; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial primary completion date: Jun 2021 ➔ Jan 2022

Clinical • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • IL10 • IL6

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=180; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial completion date: Jan 2022 ➔ Oct 2022

Clinical • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • IL10 • IL6

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial completion date: Jul 2021 ➔ Dec 2021

Clinical • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • IL10 • IL6

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=180; Recruiting; Sponsor: Janssen Research & Development, LLC; N=90 ➔ 180

Clinical • Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • IL10 • IL6

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Janssen Research & Development, LLC

Clinical • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • IL10 • IL6

A novel C2 domain binding CD33xCD3 bispecific antibody with potent T-cell redirection activity against acute myeloid leukemia. (PubMed, Blood Adv) - "Lastly, JNJ-67571244 mediated efficient cytotoxicity of cell lines and primary samples regardless of their SNP genotype status, suggesting a potential therapeutic benefit over other V-binding antibodies. JNJ-67571244 is currently in phase 1 clinical trials in patients with relapsed/refractory AML and high-risk myelodysplastic syndrome."

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