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- Title
Phase I Study of the Prolactin Receptor Antagonist LFA102 in Metastatic Breast and Castration-Resistant Prostate Cancer.
- Authors
Agarwal, Neeraj; Machiels, Jean‐Pascal; Suárez, Cristina; Lewis, Nancy; Higgins, Michaela; Wisinski, Kari; Awada, Ahmad; Maur, Michela; Stein, Mark; Hwang, Andy; Mosher, Rebecca; Wasserman, Ernesto; Wu, Gang; Zhang, Hefei; Zieba, Renata; Elmeliegy, Mohamed
- Abstract
Background. Prolactin receptor (PRLR) signaling is implicated in breast and prostate cancer. LFA102, a humanized monoclonal antibody (mAb) that binds to and inhibits the PRLR, has exhibited promising preclinical antitumor activity. Methods. Patients with PRLR-positive metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (mCRPC) received doses of LFA102 at 3-60 mg/kg intravenously once every 4 weeks. Objectives were to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) to investigate the safety/tolerability of LFA102 and to assess pharmaco-kinetics (PK), pharmacodynamics (PD), and antitumor activity. Results. A total of 73 patients were enrolled at 5 dose levels. The MTD was not reached because of lack of dose-limiting toxicities. The RDE was established at 60 mg/kg based on PK and PD analysis and safety data. The most common all-cause adverse events (AEs) were fatigue (44%) and nausea (33%) regardless of relationship. Grade 3/4 AEs reported to be related to LFA102 occurred in 4% of patients. LFA102 exposure increased approximately dose proportionally across the doses tested. Serum prolactin levels increased in response to LFA102 administration, suggesting its potential as a biomarker for PRLR inhibition. No antitumor activity was detected. Conclusion. Treatment with LFA102 was safe and well tolerated, but did not show antitumor activity as monotherapy at the doses tested.
- Subjects
BREAST tumors; METASTASIS; MONOCLONAL antibodies; PROLACTIN; PROSTATE tumors
- Publication
Oncologist, 2016, Vol 21, Issue 5, p535
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2015-0502