D7-02: Activity of BIBW2992, an oral irreversible dual EGFR/HER2 inhibitor, in non-small cell lung cancer (NSCLC) with mutated EGFR

BIBW2992 is a novel oral, potent and irreversible inhibitor of both EGFR and HER2. Here the results from a phase I study of BIBW2992 are reported. Responses were seen in 3 of 12 patients with NSCLC, and analysis of EGFR mutation status was performed in responders. Patients eligible for this phase I trial had advanced solid malignancies; prior treatment with agents targeting EGFR or HER2 was allowed. Oral BIBW2992 dose was doubled in successive cohorts until toxicity > grade 2 occurred, when escalation of no more than 50% was allowed. Sequencing of tumour DNA for EGFR and HER2 was performed in objective responders. 47 evaluable patients have been treated (24 male); median age 56 (range 31-78). The pharmacokinetics of BIBW2992 were consistent with once daily dosing. Three dose-limiting toxicities (DLT) were seen in cycle 1; one patient developed dyspnoea with interstitial changes at 30mg and fully recovered on discontinuation; two developed grade 3 acneiform rash at doses of 40mg and 50mg, which resolved on discontinuation and dose reduction. Grade 3 diarrhoea in cycle 2 in one patient at 50mg resolved on dose reduction. Other adverse events were mild (grade 1 or 2); nausea, diarrhoea, hand-foot syndrome and fatigue. Dose was escalated from 10 to 50mg. 11 patients remained on study for more than 6 months. 3/12 patients with NSCLC had confirmed partial response: Tabled 1agesexhistologydose(daily)months on studyEGFR genotype55Fadeno10mg26KEP……..SPRANKEILD67Fadeno40mg20K……….TSPRANKEILD38*Madeno40mg7+−*never smokerwild typeKELREATSPKANKEILDUpdated clinical data will be presented at the meeting. Open table in a new tab Updated clinical data will be presented at the meeting. The recommended phase II BIBW2992 dose of 50mg daily is well tolerated. Durable partial responses were seen in 25% of NSCLC patients in this study, with at least 2 of them having deletions in EGFR exon 19. Mutation in exon 19 is known to be more common in females, never smokers and in patients with adenocarcinoma, consistent with our data. Further studies in this tumour type are warranted.