A phase I dose escalation study of BIBF 1120 combined with FOLFOX in metastatic colorectal cancer (mCRC) patients (pts).

Abstract

e14054 Background: BIBF 1120 is a potent oral triple angiokinase inhibitor targeting VEGFR 1–3, PDGFR α and β and FGFR 1–3. BIBF 1120 has the potential to be an effective treatment for many solid tumors and is currently in phase III clinical development. It was well tolerated at the dose of 200 mg bid when combined with chemotherapies such as pemetrexed, docetaxel, paclitaxel/carboplatin. It has already shown activity in mCRC patients (pts). We report the results of a Phase I study investigating the tolerability of BIBF 1120 at two different dosages combined with a modified FOLFOX 6 regimen in chemotherapy-naïve mCRC pts. Methods: Main eligibility criteria were performance status (PS) ≤ 2, no prior palliative chemotherapy, adequate biological functions and measurable lesions. The first dose cohort received 150 mg bid BIBF 1120. If well tolerated, this dose was escalated to 200 mg bid. A modified FOLFOX 6 regimen was given concomitantly at a fixed dose, on a 2-weekly treatment cycle basis in both cohorts: 5FU at 400 mg/m2 bolus and 2400 mg/m2 continuous infusion over 46 hours, oxaliplatin at 85 mg/m2 over 2 hours and l-leucovorin at 200 mg/m2 or d,l-leucovorin at 400 mg/m2 over 2 hours. BIBF 1120 PK data were collected during the three first cycles. Dose-limiting toxicities (DLTs) were assessed during the first two cycles. Results: In total, 15 mCRC pts (9 male and 6 female) were enrolled. The median age was 62 years (47–76) and the median PS was 0 (0–2). No pts had prior adjuvant chemotherapy and 73% of pts had abnormal LDH at screening. Only 12 pts were evaluable for the determination of the DLTs over the first two cycles. 3 and 9 pts have been treated with 150 mg bid and 200 mg bid, respectively. Two DLTs occurred, one in the low-dose cohort – a reversible grade 3 diffuse maculopapular skin rash – and one in the high-dose cohort – a reversible grade 3 transaminase elevation with a simultaneous reversible grade 1 bilirubin increase. No other NCI-CTCAE grade 3 or 4 adverse events were observed during the first 2 cycles. Conclusions: This study shows that BIBF 1120 at the dose of 200 mg bid can be safely combined with therapeutic doses of a modified FOLFOX 6 regimen; this combination is being further evaluated in a phase II study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Amgen, AstraZeneca, Fresenius, Merck Serono, MSD, Pfizer, Roche, sanofi-aventis Amgen, Merck Serono, Pfizer, Roche Boehringer Ingelheim