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STEAP1 as a predictive biomarker for antibody-drug conjugate (ADC) activity in metastatic castration resistant prostate cancer (mCRPC).

2015; Lippincott Williams & Wilkins; Volume: 33; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2015.33.15_suppl.5029

1527-7755

Daniel C. Danila, Martin Fleisher, Jorge A. Carrasquillo, Houston Gilbert, Michael J. Morris, Lawrence Bellomo, Petrus J. Hendrikx, Edith Szafer‐Glusman, Amrita Herkal, Chintan Patel, Nicole A. Schreiber, Kristen Curtis, Daniel Maslyar, Vanessa Lemahieu, Bernard M. Fine, Michael Mamounas, Alexander Ungewickell, Mark R. Lackner, Howard I. Scher, Omar Kabbarah,

Radiopharmaceutical Chemistry and Applications

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 (> 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 STEAP1 +ve signal in EpCAM +ve events by FACS in 48% (14/29, 30-67%), confirmed by RT-PCR, along with AR (androgen receptor) and KLK3 expression. STEAP1 +ve events were EpCAM +ve in a range from 0-74%. ADC activity by IHC and CTC is shown in Table. For STEAP1 iPET imaged pts, PSA decline by ≥ 50% was noted in 4/14 (29%, 8-58%) pts. Time on treatment correlated with bone metastasis SUVmax (r = 0.63). All 8 PET-guided biopsies were confirmed STEAP1 IHC 2+/3+. Conclusions: The best evidence for STEAP1 ADC activity by PSA declines, time on study, and CTC conversion was seen in high expression tumors. Pts with IHC 2+/3+ tumors are being prospectively selected in an expansion study where predictive biomarkers are studied as companion diagnostics. STEAP1 IHC score and treatment response. IHC Score Pts Observed/ Total (%, 95% CI) PSA decline by ≥ 50% > 6 months on treatment CTC conversion from U to F 1+ 5/45 (11%, 4-24%) 1/5 (20%, 1-72%) 0/5 (0%, 0-52%) 1/3 (33%, 1-91%) 2+ 27/45 (60%, 44-74%) 4/27 (15%, 4-34%) 6/27 (22%, 9-43%) 7/14 (50%, 23-77%) 3+ 13/45 (29%, 16-44%) 5/13 (39%, 14-68%) 6/13 (46%, 19-75%) 3/3 (100%, 29-100%)