NKTR-102 in patients with platinum-resistant ovarian cancer (PROC): Modeling CA125 response and its correlation with tumor response.

5048 Background: NKTR-102 is a unique topoisomerase 1 inhibitor that provides continuous exposure to SN38. In heavily pretreated pts with PROC (median of 3 prior therapies; 27 pts were platinum refractory), 145 mg/m2 NKTR-102 given q14d or q21d demonstrated significant anti-tumor activity (JCO 28:7s, 5013). We present a PK/PD model for CA125 kinetics that can be used to project GCIG response as an aide to selecting dose and schedule. Methods: Data from 55 pts with PROC and elevated CA125 (median baseline = 515 U/mL) were fit with a PK/PD model developed to correlate CA125 dynamics with SN38 conc-time profiles predicted from individual pt dosing history: d[CA125]/dt = Kin*exp(beta*t)*(1-[SN38]/(IC50+[SN38]))-Kout*[CA125]. Results: CA125 profiles were well described by the model, with a population mean SN38 IC50 of 1.1 ng/mL. Typical min and max SN38 conc during treatment were 1.5 and 3 ng/mL for q14d and 0.9 and 2.4 ng/mL for q21d, indicating that both schedules resulted in SN38 exposure near the IC50. The...