PF-08046040 / BeOne Medicines, Pfizer - LARVOL DELTA

TNF-α and IFN-γ differentially regulate AML cell susceptibility to CD70-antibody-mediated cytotoxicity. (PubMed, J Immunother Cancer) - "CD70 is a promising target for NK cell-based immunotherapy in AML. However, IFN-γ-dependent upregulation of HLA molecules on AML cells contributes to resistance to ADCC. These findings underscore the need for rationale combination strategies in clinical trials to overcome this inducible immune escape mechanism."

IO biomarker • Journal • Acute Myelogenous Leukemia • Genetic Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Primary Immunodeficiency • CD33 • CD70 • HLA-C • HLA-E • IFNG • KIR2DS2 • KLRC1 • TNFA

PF-08046040 (SEA-CD70), a Nonfucosylated CD70-Directed Antibody, in Combination with Azacitidine for Patients with Myelodysplastic Syndromes (MDS): A Phase 1 Dose-Finding and Dose Expansion Study (ASH 2024) - P1 | "Preliminary efficacy was observed for pts with HR-MDS, with 16% of pts subsequently receiving transplant for both 10 mg/kg and 20 mg/kg dose cohorts. Results support the continued development of SEA-CD70 + AZA for pts with myeloid malignancies."

Clinical • Combination therapy • IO biomarker • P1 data • Acute Myelogenous Leukemia • Anemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • CD27 • CD70

SGNS70-101: A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1 | N=178 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Jun 2027 ➔ Jun 2028 | Trial primary completion date: Jun 2026 ➔ Jun 2027

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

SGNS70-101: A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1 | N=178 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Nov 2026 ➔ Apr 2027 | Trial primary completion date: Dec 2024 ➔ Apr 2026

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

Pfizer Showcases Scientific Leadership in…Blood Disorders…at ASH… (Pfizer Press Release) - "Key ASH Presentations: Data from more than 75 company-sponsored, investigator-sponsored, and collaborative research abstracts will be presented at ASH, including updated analyses from the pivotal ECHELON-3 trial supporting the clinical benefit of ADCETRIS (brentuximab vedotin) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). New data for ELREXFIO (elranatamab-bcmm) in relapsed/refractory multiple myeloma (RRMM) will also be presented from the pivotal MagnetisMM-3 trial, as well as Phase 1 combination data from the MagnetisMM-20 trial. Pfizer will also present updates from its growing Hematology-Oncology pipeline, which includes next-generation CD30 antibody-drug conjugates and other novel and differentiated molecules, including the first presentation of combination data for SEA-CD70 in high-risk myelodysplastic syndromes."

Clinical data • Diffuse Large B Cell Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome

[VIRTUAL] A Phase 1 Study of Sea-CD70 in Myeloid Malignancies (ASH 2020) - P1 | "Methods SGNS70-101 is a phase 1, open-label, multicenter, dose-escalation, and cohort expansion study designed to establish the safety, tolerability, and preliminary activity of SEA-CD70 in pts with myeloid malignancies (NCT04227847). Once dose escalation is complete and the recommended monotherapy dose is identified, combination cohorts will be considered in AML and MDS. The study is currently enrolling with sites opening in the US and EU."

IO Biomarker • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD27 • CD70

The two sides of the coin: pro-inflammatory stimuli lead to upregulation of CD70 in AML, but also reduce NK-cell-based immunotherapy efficacy. (SITC 2022) - "NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) assays utilizing a sugar-engineered anti CD70 antibody with a nonfucosylated Fc backbone (SEA-CD70) were performed against AML cell lines with varying CD70 expression levels and primary AML cells (n=6)...However, these pro-inflammatory stimuli inhibit NK-mediated ADCC activity. This data warrant future studies to understand how modulation of the TME may be utilized as a strategy to enhance target expression without negatively impacting effector cell functions."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Oncology • CD33 • CD70 • IFNG • PTPRC • TNFA

A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Seagen Inc. | N=60 ➔ 140 | Trial completion date: Oct 2024 ➔ Nov 2026 | Trial primary completion date: Nov 2022 ➔ Dec 2024

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Seattle Genetics, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • PML

[VIRTUAL] Potential of Sea-CD70 for the Treatment of Myeloid Leukemia (ASH 2020) - "In vivo, SEA-CD70 delayed tumor growth and increased survival in subcutaneous AML xenograft mouse tumor models both as a single agent and when combined with standard of care (SOC) agents. Overall, our data highlight the therapeutic potential of SEA-CD70 for the treatment of AML and MDS patients."

Aplastic Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Leukemia • Oncology • CD27 • CD70 • TNFA

A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1; N=60; Not yet recruiting; Sponsor: Seattle Genetics, Inc.; Trial completion date: Mar 2024 ➔ Oct 2024; Initiation date: Jan 2020 ➔ Aug 2020; Trial primary completion date: Apr 2022 ➔ Nov 2022

Clinical • Trial completion date • Trial initiation date • Trial primary completion date

A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Seattle Genetics, Inc.

Clinical • New P1 trial