A blinded placebo (P)-controlled phase I/II dose-escalation study (DES) of brivanib (B), an oral selective dual inhibitor of FGF and VEGF signaling, in combination with cetuximab (C) and irinotecan (I) in patients (pts) with KRAS wild-type (KWT) advanced or metastatic colorectal cancer (amCRC): Safety, tolerability, and pharmacokinetics (PK) findings.

e13552 Background: B has therapeutic potential in a variety of tumors. B+C treatment is currently being tested in phase III in refractory amCRC. An innovative phase I design was used to separate specific B toxicity (thrombosis-related events [TRE]) from the background rate. Methods: A blinded P-controlled phase I/II DES of B+C+I (BCI) was conducted in pts with KWT amCRC. A minimum of 4 pts/cohort were treated with BCI and 2 pts/cohort were treated with P+C+I (PCI). Standard full-dose I (q3w) and C (qw) were combined with escalating doses of B (200, 400, 600, 800 mg) PO qd. Results: 30 pts were treated with 200 (6), 400 (8), 600 (10), or 800 (6) mg of BCI or PCI for a median of 14 weeks (range 1–38). One dose-limiting toxicity (DLT), grade III diarrhea, occurred at 600 mg. Blinded safety data on 200, 400, and 600 mg (8/10 pts) are presented. The 800 mg cohort is ongoing; a maximum tolerated dose has not yet been reached. Adverse events (AEs; regardless of relationship) occurred in 17/21 pts and are consist...