A phase (Ph) Ib study of irinotecan (IRI), levofolinate (LV), and 5-fluorouracil (5-FU) (FOLFIRI) plus ramucirumab (RAM; IMC-1121B) drug product in Japanese (JP) patients (pts) with metastatic colorectal carcinoma (mCRC) progressive during or following first-line therapy with bevacizumab (BEV), oxaliplatin (OXALI), and a fluoropyrimidine (FP) (CP12-1029/NCT01286818).

Abstract

591 Background: Vascular endothelial growth factor (VEGF) and the VEGF receptor-2 (VEGFR-2) regulate angiogenesis and are overexpressed in CRC. RAM is a fully human IgG1 monoclonal antibody VEGF-receptor 2 antagonist. We assessed the safety of RAM + FOLFIRI among JP mCRC pts. Methods: Eligible pts had measurable or nonmeasurable disease, ECOG PS 0-1 with disease progression during or within 6 mos following 1st-line therapy with BEV, OXALI, and a FP. Pts received 8 mg/kg RAM IV every 2 wks + FOLFIRI (IRI: 180 mg/m2, LV: 200 mg/m2, 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46-48 hrs). Dose-limiting toxicities (DLTs) were assessed Cycle 1 Day 1 to Cycle 3 Day 1. We assessed the safety of RAM + FOLFIRI among JP mCRC pts to support the participation of Japan in a global Ph 3 mCRC study. Results: 6 pts were treated; all pts completed study as of 3/19/2012. Median age was 62 yrs (range 48-71). 4 pts had colon cancer and 2 pts had rectal cancer . 1 of 6 pts experienced a DLT (Grade [G] 2 proteinuria and G4 neutropenia resulting in dose delay >2 wks). All 6 pts (100%) experienced at least one G3 adverse event (AE): neutropenia (5 pts; 83%), proteinuria (2 pts; 33%), anemia, thrombocytopenia, hypertension (1 pt each, 17%). 3 pts (50%) experienced G4 neutropenia. 2 pts discontinued (D/C) RAM due to G2 and G3 proteinuria, respectively; 1 pt D/C FOLFIRI due to G3 neutropenia. There were no serious AEs or deaths. Best overall response: 1 PR (17%), 4 SD (67%), 1 PD (17%). Median PFS: 7.3m (range: 1.25-10.91m; 95% CI: 1.2 – 10.9). As of 9/24/2012, 57 JP pts have been enrolled into ongoing P3 study I4T-MC-JVBB. Conclusions: RAM + FOLFIRI were reasonably tolerated and demonstrated anti-tumor activity in JP mCRC pts previously treated with BEV, OXALI, and a FP. The incidence of proteinuria in this small cohort of JP pts appears higher than that observed in other studies evaluating RAM to date. These safety data supported the enrollment of JP pts into an ongoing global P3 mCRC study. Clinical trial information: NCT01286818.