First-in-human phase I trial of prostate-specific membrane antigen antibody drug conjugate (PSMA ADC) in taxane-refractory prostate cancer.

Abstract

TPS245 Background: PSMA is a type II transmembrane glycoprotein with abundant and restricted expression on prostate cancer cells. PSMA ADC comprises a monoclonal antibody (mAb) to PSMA linked to the antitubulin agent monomethyl auristatin E (MMAE). PSMA ADC demonstrated potent activity against human prostate tumors in preclinical studies (Ma et al, Clin Canc Res 12:2591). This report describes an ongoing phase I dose escalation study of PSMA ADC in patients (pts) with progressive taxane refractory metastatic prostate cancer (metCRPC). The goals of the trial are to determine a maximum tolerated dose (MTD), identify potential dose limiting toxicities, describe the pK profile of free MMAE and the parent compound, and detect potential antitumor activity of PSMA ADC. Methods: Eligible pts are ≥18 years with metCRPC after failure of a taxane-containing regimen and ECOG status of 0 or 1. PSMA ADC is administered by IV infusion Q3W for up to 4 cycles. Adverse events, pK, PSA, circulating tumor cells, clinical disease progression, and immunogenic response to PSMA ADC or its components are assessed. Serum concentrations of study drug (PSMA ADC) and total antibody (PSMA mAb + PSMA ADC) are measured by an enzyme-linked immunosorbent assay (ELISA) method and serum concentrations of free toxin (MMAE) are measured by a liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method. Using a modified Fibonacci sequence, dosing began at 0.4 mg/kg in the first cohort. Pts perceived to be benefitting from treatment may be enrolled in an extension study of PSMA ADC at the same dose. Current Status:Fifteen patients have been treated to date; Cohort 1 (0.4 mg/kg), 3 pts; Cohort 2 (0.7 mg/kg), 3 pts; Cohort 3 (1.1 mg/kg), 3 pts; Cohort 4 (1.8 mg/kg), 6 pts. Two pts have enrolled in the extension study. Enrollment is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Progenics Pharmaceuticals, Inc. Progenics Pharmaceuticals, Inc. Progenics Pharmaceuticals, Inc. Progenics Pharmaceuticals, Inc.