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Title: A 2-Week-On, 2-Week-Off Schedule Appears Optimal for BIBW 2992 in Advanced Solid Tumors: Presented at AACR-NCI-EORTC

"A 2-Week-On, 2-Week-Off Schedule Appears Optimal for BIBW 2992 in Advanced Solid Tumors: Presented at AACR-NCI-EORTC"

By Maggie Schwarz PHILADELPHIA, PA -- November 21, 2005 -- The investigational agent BIBW 2992 at a dose of 70 mg appears safe in patients with solid tumors and the adverse effects can be easily controlled with loperamide and minocycline, according to a phase 1 and pharmacological dose escalation study. Ferry ALM Eskens, MD, PhD, Professor of Clinical Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands, presented the results on November 16[^th at the International Conference on Molecular Targets and Cancer Therapeutics.

The conference was organized jointly by the American Association for Cancer Research, National Cancer Institute, and the European Organisation for Research and Treatment of Cancer (AACR-NCI-EORTC).

BIBW 2992 is a highly selective potent irreversible dual inhibitor of the intracellular tyrosine kinase activity of epidermal growth factor receptor 1 (EGFR-1) and 2 (HER2). It inhibits EGF-induced receptor phosphorylation and cellular proliferation in the low nanomolar range.

Dr. Eskens and colleagues enrolled patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of BIBW 2992 administered once daily (OD) for 14 days followed by 14 days off treatment. The also evaluated results for preliminary evidence of anti-tumor activity.

He presented the results of the ongoing study in 34 patients enrolled so far. Median patient age was 57 years, and ranged from 18 to 80 years.

Patients had a histologically or cytologically confirmed diagnosis of solid malignant tumor that was refractory to standard therapies. Preferably patients with tumours historically known to express EGFR and/or HER2 were eligible.

Patients were treated for 2 weeks followed by a 2-week rest. These cycles could be repeated if the patient was not progressing. Patients with stable disease after 6 courses of treatment were allowed to continue in an extension study.

No complete or partial responses were seen, but seven patients had stable disease that lasted 4 four or more courses of treatment.

Dose-limiting toxicity consisted of skin toxicity and diarrhea. The investigators recommended a 70 mg dose, at which diarrhea and skin toxicity can be controlled using loperamide and minocycline.

They concluded that BIBW 2992 was safe in patients given a 2-week-on, 2-week-off schedule.

[Presentation title: A Phase I Dose Escalation Study of BIBW 2992, an Irreversible Tyrosine Kinase Inhibitor of Epidermal Growth Factor Receptor 1 (EGFR-1) and 2 (Her2) in a 2 Week on 2 Week off Schedule in Patients with Advanced Solid Tumors. Abstract A235]

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