Use of BIBW 2992, a novel irreversible EGFR/HER2 TKI, to induce regression in patients with adenocarcinoma of the lung and activating EGFR mutations: Preliminary results of a single-arm phase II clinical trial

Abstract

8026 Background: BIBW 2992 is a highly potent dual EGFR and HER2 inhibitor with preclinical activity in cell lines harboring EGFR activating mutations (H1650, IC50=0.7 nM) as well as those with T790M mutations (H1975, IC50=99 nM). A phase II study of BIBW 2992 in chemotherapy-treated EGFR tyrosine kinase domain mutation positive patients is being conducted. Methods: Two-stage study conducted in Taiwan and US with first analysis planned when 40 patients have completed one course of treatment(28 days); if 16 or more patients respond, accrual will expand to a total of 80 patients. Eligibility criteria include stage IIIB/IV lung adenocarcinoma, EGFR mutation present in exons 18–21 (tested by direct sequencing), measurable disease, ECOG performance status of 0–2, adequate end organ function and progressive disease following neoadjuvant/adjuvant chemotherapy or one chemotherapy regimen for metastatic disease. Patients receive 50 mg BIBW 2992 once daily until disease progression. Tumor assessments are performed every course for 3 courses and every 2 courses thereafter. The primary endpoint is objective response rate. Results: Samples from 48 consented patients from Taiwan were sequenced. Twenty-one (43.7%) had detectable EGFR mutations, including del19 (N=10), L858R (N=7) and other mutations (N=4). Ten patients started treatment. Preliminary analysis of the first 6 patients (3F/3M) who were treated for at least 28 days and had tumor response assessment is reported here. Five patients had PR (3 del19;1 L858R and 1 with G719S/S768I), and one had SD (L858R). Tumor regressions were readily observed on plain chest X-ray on day 8 of treatment in 5 patients. Most frequently occurring side effects included skin toxicity (Grade 3 in one patient) and diarrhea (Grade 3 in two patients). One patient had dose reduction to 30 mg per day due to Grade 3 hand-foot syndrome and paronychia; one to 40 mg per day due to Grade 3 diarrhea. Conclusions: BIBW 2992 50 mg per day induced rapid responses and seems promising in NSCLC patients harboring EGFR activating mutations. Manageable cutaneous toxicity and diarrhea are the main adverse events. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim