Steap1 As A Predictive Biomarker For Antibody-Drug Conjugate (Adc) Activity In Metastatic Castration Resistant Prostate Cancer (Mcrpc).

5029 Background: STEAP1 is overexpressed in mCRPC and is an ADC target. STEAP1 expression in tissue assayed by IHC, protein and mRNA expression levels in circulating tumor cells (CTC) and by 89Zr-labeled anti-STEAP1 antibody uptake by iPET. Methods: Patients (pts) with progressive mCRPC received doses of the ADC ranging from 0.3 to 2.8 mg/kg once every three weeks. Antitumor activity was assessed by PSA declines, time on study and changes in CTC number (CellSearch). STEAP1 expression in tumor tissue by a validated IHC assay was used as reference biomarker on a scale of 0 (not detected) to 3+ (highest expression). Protein and mRNA expression in CTCs was explored by FACS and RT-PCR, and standardized uptake values (SUV) of 89Zr-labeled anti-STEAP1 antibody by iPET. Results: At doses of ≥ 2 mg/kg, a ≥ 50% PSA decline was observed in 22% (10/45, 11-37%), and CTC conversions from unfavorable (u003e 5 cells) to favorable (4 or fewer/7.5 ml of blood) in 55% (11/20, 32-77%) of cases. CTC showed a readily detectable ST...