Pharmacokinetics (PK) and exposure-response (ER) of rilotumumab (Rmab) in patients (pts) with small-cell lung cancer (SCLC).

7593 Background: Rmab is a fully human monoclonal antibody against hepatocyte growth factor that was evaluated as a first-line treatment for extensive-stage SCLC in a phase 1b/2 trial (J Thorac Oncol. 2013;8(S2):O21.05). That trial did not show meaningful improvements in progression-free survival (PFS) or overall survival (OS). We characterized Rmab PK in pts with SCLC and performed an ER analysis that related PK to tumor size (TS), PFS, and OS. Methods: Rmab population PK (PPK) and ER were assessed in 132 pts with SCLC who were randomized 1:1 to receive either Rmab (15 mg/kg) or placebo, with etoposide plus carboplatin/cisplatin every 3 weeks (Q3W). A PPK model was developed using data from phase 1 and earlier phase 2 studies. TS vs time was characterized using a tumor dynamic model, and time to tumor growth (TTG) and TS ratios (the ratios of TS at 6, 9, or 12 weeks to TS at baseline) were derived from this model. The relationships between PFS/OS and baseline pt characteristics, exposure metrics, and tum...