Abstract 4310: Predictive biomarkers of tumor sensitivity to STEAP1 antibody-drug conjugate (ADC) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

ADCs hold promise for enhancing the therapeutic index of cytotoxics. STEAP1 is overexpressed in mCRPC and is the target of an ADC currently under clinical development. To identify pts most likely to benefit from the ADC, we explored STEAP1 expression as a predictive biomarker in tumor tissue using a CLIA-certified IHC assay, and on circulating tumor cells (CTCs) in blood using the CellSearch and EPIC platforms. Sixty pts with progressive mCRPC received doses ranging from 0.3 to 2.8 mg/kg once every three weeks. Response was defined as a ≥50% decline in PSA from baseline, and time on study for >6 months was consistent with continued clinical benefit. At doses of ≥2 mg/kg, the response rate (RR) was 10/45 (22%, 95% CI 9.9-34.1) and was highest in the STEAP1 IHC 3+ group, as was the fraction of patients who remained on study for >6 months. At ≥2 mg/kg, 20/45 pts (44%, 95% CI 29.5-58.5) had unfavorable CTC counts of ≥5/7.5mL at baseline and were considered evaluable. After treatment, conversions from unfavorable to favorable CTC counts of 6 months on treatment(%, 95% CI)(%, 95% CI)(%, 95% CI)1+5/45 (11%, 1.9-20.1)1/5 (20%, -15.1-55.1)0/5 (0%)2+27/454/276/27(60%, 45.7-74.3)(15%, 1.5-28.5)(22%, 6.4-37.6)3+13/455/136/13(29%, 15.7-42.2)(39%, 12.5-65.5)(46%, 18.9-73.1)CTC Analysis and Treatment ResponseCTC endpointTime Point & CTC Conversion vs. baselinePts Observed/TotalPSA decline by ≥50% from baseline>6 months on treatment(%, 95% CI)(%, 95% CI)(%, 95% CI)CTC countsBaseline ≥5/7.5mL20/456/206/20(at ≥2 mg/kg)(44%, 29.5-58.5)(30%, 9.9-50.1)(30%, 9.9-50.1)Baseline