On November 4, 2020 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune disease, reported that data from the ongoing Phase 1 dose-escalation study of vibecotamab (XmAb14045), a CD123 x CD3 bispecific antibody, in patients with relapsed/refractory acute myeloid leukemia (AML) will be presented in an oral session at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Sunday, December 6, 2020 (Press release, Xencor, NOV 4, 2020, View Source [SID1234569874]).

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"Data from the Phase 1 study of vibecotamab suggest that patients with AML having low baseline disease burden and specific T-cell signatures may be more likely to respond to treatment with vibecotamab. The primary toxicity, CRS, is generally mild-to-moderate in severity when observed and is manageable," said Allen Yang, M.D., Ph.D., senior vice president and chief medical offer at Xencor. "We continue to optimize dosing regimen in this study, and along with our partner Novartis, we are planning our next clinical trials to develop vibecotamab in patients, for whom an intermittently dosed, CD123-targeting antibody could be a needed therapeutic option."

Key Highlights from the Abstract

The accepted abstract is available on the ASH (Free ASH Whitepaper) conference website.

At data cut off for submitting the abstract, 104 patients with AML, one patient with B cell acute lymphoblastic leukemia and one patient with chronic myeloid leukemia had received vibecotamab. Patients had a median age of 63 years and were heavily pretreated, having a median of three prior therapies, and 30% (n=32/106) had undergone prior allogeneic stem cell transplantation.
Patients received doses of vibecotamab ranging from 0.003 mcg/kg to 12 mcg/kg. The recommended initial priming dose was determined to be 0.75 mcg/kg. A maximum tolerated dose (MTD) was not reached.
Cytokine release syndrome (CRS) was the most common toxicity occurring in 58% of patients (n=62), and 8% of patients (n=9) experienced CRS at Grade 3 or higher. The majority of CRS was observed on the first dose and was generally manageable with premedication. Additional adverse events consistent with CRS but not reported as such, including chills, fever, tachycardia and hypotension, were reported in an additional 24% of patients. No myelosuppression requiring dose modification or evidence of tumor lysis syndrome was observed.
At dose levels of at least 0.75 mcg/kg (n=51), two patients achieved complete remission (CR), three patients achieved a CR with incomplete hematologic recovery, and two patients or morphologic leukemia-free state (ORR=14%).
Patients with responses were characterized by lower disease burden and specific T-cell subtypes.
Presentation Details

Abstract: 460
Title: Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of Vibecotamab (XmAb14045), a CD123 x CD3 T Cell-Engaging Bispecific Antibody; Initial Results of a Phase 1 Study
Session: 613. Acute Myeloid Leukemia: Potpourri of Potential Practice Changing Studies
Date & Time: Sunday, December 6, 2020, 2:30 p.m. PST
About Vibecotamab

Vibecotamab (XmAb14045) is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on vibecotamab. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by vibecotamab activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.