Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study
Journal
Cancer discovery
Journal Volume
14
Journal Issue
1
Date Issued
2024-01-12
Author(s)
Kelly, William K
Danila, Daniel C
Lee, Jae-Lyun
Matsubara, Nobuaki
Ward, Patrick J
Armstrong, Andrew J
Pook, David
Kim, Miso
Dorff, Tanya B
Fischer, Stefanie
Lin, Yung-Chang
Horvath, Lisa G
Sumey, Christopher
Yang, Zhao
Jurida, Gabor
Smith, Kristen M
Connarn, Jamie N
Penny, Hweixian L
Stieglmaier, Julia
Appleman, Leonard J
Abstract
Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development.
Type
journal article