478P - Phase I Safety and Tolerability of Once Daily Oral Afatinib (A) (BIBW 2992) in Combination with Gemcitabine (G) in Patients (PTS) with Advanced Solid Tumours

Abstract

ABSTRACT Background A is an orally bioavailable, irreversible, ErbB Family Blocker. This open label, Phase I, dose escalation trial investigated the safety, tolerability and pharmacokinetics of A in two parallel dose cohort expansion parts, in combination with either G (Part A) or docetaxel (Part B) in pts with relapsed or refractory solid tumours. Preliminary results from Part A are presented here. Methods Eligible pts (confirmed diagnosis of advanced solid tumours, Eastern Cooperative Oncology Group Performance Status 0–1) received once-daily, oral dosing of A in combination with G, given intravenously at Day 1 and at Day 8 of every 3 week cycle. Dosing of A started on Day 2 of Cycle 1. The primary objective was to establish the maximum tolerated dose (MTD) based on the occurrence of dose limiting toxicities (DLTs) observed in Cycle 1. Dose escalation was performed with cohorts of 3–6 pts using a 3 + 3 design. Initial starting dose level was A 30 mg/day and G 1000mg /m2, escalating up to A 50 mg/day and G 1250 mg/m2, until the MTD was reached, and followed by a pharmacokinetic expansion cohort of 12 pts at the MTD level. Results Nineteen pts were treated in the escalation part of the study with the following baseline characteristics: mean age (53.7 years), female (63.2%) and number of prior chemotherapies (≤2: 26%; >2: 74%). In Cycle 1, DLTs were experienced by one pt out of six receiving A 30 mg and G 1250 mg/m2, and in two pts at a dose level of A 40 mg/day and G 1250 mg/m2. Adverse events (AEs) observed in most pts were diarrhoea (89.5%) and rash (63.2%). MTD was exceeded at a dose level of A 40 mg/day and G 1250 mg/m2. An intermediate dose level of A 40 mg/day and G 1000 mg/m2 is currently under evaluation with two pts enrolled to date. Conclusions In pts with relapsed or refractory advanced solid tumours, the combination of A with G is well tolerated, with manageable AEs. Dose finding is ongoing and MTD, safety profile and preliminary evidence of activity are anticipated to be reported at time of presentation. Disclosure J. Bennouna: I have received honoraria from roche, boehringer ingelheim, and amgen for advisory board. It is for myself. H. De Mont-Serrat: Employee of Boehringer Ingelheim. I. Tschoepe: Employee of Boehringer Ingelheim. P. Squiban: Employee of Boehringer Ingelheim. All other authors have declared no conflicts of interest.