Novel Antibody-Drug Conjugate in Castration-Resistant Prostate Cancer
Posted: Wednesday, April 17, 2019
ASG-5ME, an antibody linked to the drug monomethyl auristatin E (MMAE), will not be further developed for the treatment of castration-resistant prostate cancer, based on the toxicity results of a phase I study. The research was published in Investigational New Drugs by Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center, and colleagues.
The phase I trial included 46 patients with metastatic castration-resistant prostate cancer: 26 patients in the dose-escalation cohort, and 20 in the dose-expansion cohort. All patients but one were white. Patients received an infusion of ASG-5ME every 3 weeks. The primary objective was to determine the maximum tolerated dose and the recommended dose for a phase II trial. Secondary endpoints included safety, antitumor activity, pharmacokinetic properties, and immunogenicity.
There were two deaths related to treatment. A 64-year-old man experienced grade 3 hyperglycemia, renal insufficiency, and leukopenia, then 2 weeks later an ileus, profound hypertension, and renal failure. A 53-year-old man had grade 3 hyperglycemia complicated by Streptococcus viridans bacteremia, which led to sepsis and organ failure. Four patients experienced dose-limiting toxicities, including grade 3 abdominal pain, diarrhea, fatigue, constipation, hypoxia, and troponin elevation; and grade 4 neutropenia and hyponatremia. More than half of evaluable patients (52%) had stable disease or a partial response to therapy.
ASG-5ME will not be developed further for castration-resistant prostate cancer. In the trial, ASG-5ME “was associated with significant toxicities” and had a “narrow therapeutic index,” the authors wrote.
Disclosure: The study authors’ disclosure information may be found at link.springer.com.
