Monotherapy treatment with the triple angiokinase inhibitor1 BIBF 1120 (planned tradename Vargatef ™) offers promising efficacy and is well tolerated in patients with advanced, relapsed non small cell lung cancer (NSCLC), according to results from a phase II study in patients with lung cancer2. Of particular note were results from a subset of 57 patients with 'good disease state' (ECOG performance status of 0 or 1): these patients experienced longer overall survival (median overall survival was 9.5 months), longer progression-free survival (PFS; median PFS was 2.9 months) and a higher stable disease rate of 59% compared with the overall study population. The results were presented today by Dr Joachim von Pawel from Asklepios Fachkliniken München-Gauting, Germany, at the 1st European Lung Cancer Conference jointly organized by IASLC and ESMO in Geneva, Switzerland.

BIBF 1120, administered as a capsule taken twice daily, is currently being developed by Boehringer Ingelheim and is one of the company's most advanced molecules within the cancer development portfolio. BIBF 1120 is a novel triple angiokinase inhibitor that simultaneously inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs) and fibroblast growth factor receptors (FGFRs)1 all of which are crucially involved in the formation of blood vessels.

Commenting on these results, Dr von Pawel stated in Geneva: "This study is very encouraging because it tells us that BIBF 1120 has good efficacy when administered on its own. The substantial clinical effect observed in the subset of 57 patients with 'good' performance status (ECOG 0 - 1) is very notable and gives us great impetus to continue fully exploring the potential of this molecule." BIBF 1120 was also well tolerated by patients in this study, which is a very important consideration for cancer patients and their physicians. "The most important clinical question for us to address now is how much benefit patients may derive from BIBF 1120 treatment and the place this potential medicine may have in the cancer clinic of the future," he added.

Study design and results

This phase II study investigated the efficacy of BIBF 1120 in 73 patients with an ECOG score of 0 - 2 with locally advanced or metastatic NSCLC (stage 11B/IV)2. Patients with all histologies were eligible to enrol. All patients in the study had previously received at least one line of platinum-based therapy. The primary endpoints were PFS and objective tumour response (measured by RECIST criteria). Secondary endpoints included overall survival (OS) and safety. Patients were randomized to receive either BIBF 1120 250 mg capsule twice daily (n=36) or 150 mg capsule twice daily (n=37). Results reported were:

All patients, ECOG 0 - 2 (n=73):

-- Median PFS was 1.7 months in the overall study population, which included 16 patients with ECOG PS 2. Nearly one in two patients (48%) experienced disease control (defined as Partial Response [PR] + Complete Response [CR] + Stable Disease [SD]). There was no difference in efficacy between the two dose treatment arms.

-- Median OS of all patients was 5.5 months.

ECOG performance status 0 or 1 (n=57):

BIBF 1120 showed a substantial clinical effect in the subset of 57 patients with 'good' performance status (ECOG 0 - 1):

-- Median PFS was 2.9 months and disease control rate was 59%; there was no difference between both treatment arms.

-- Median OS in this group was 9.5 months.

The study authors reported that BIBF 1120 administered orally twice daily was generally well tolerated. The most frequent adverse events reported in this study were nausea, diarrhoea and vomiting, and they were mostly mild to moderate.

Dr Andreas Barner, Vice Chairman of the Board of Managing Directors at Boehringer Ingelheim, commented: "These new BIBF 1120 phase II data, coupled with evidence from previous studies3,4 that show BIBF 1120 is well tolerated in combination with standard lung cancer treatments, gives us great confidence in moving forward with further investigations of BIBF 1120 in lung cancer. We are pleased to report we are making great progress in our oncology research programme and we look forward to presenting further data from our franchise during 2008."

About BIBF 1120

BIBF 1120 is a novel triple angiokinase inhibitor that simultaneously inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs) and fibroblast growth factor receptors (FGFRs)1. These growth factors and receptors play an important role in angiogenesis; their inhibition plays a critical role in the prevention of tumour growth and spread.

To date, more than 400 patients have been treated with BIBF 1120 through enrolment in phase I and phase II clinical trials. In two phase I studies3,4, the dose for BIBF 1120 in combination with pemetrexed or carboplatin/paclitaxel has been determined to be 200 mg twice daily. BIBF 1120 was well tolerated by patients in both studies.

References:

(1) Hilberg F et al. Eur J Cancer Suppl. 2004;2:50.

(2) von Pawel J et al. Efficacy, Safety And Pharmacokinetic (PK) Results Of A Phase II Study With The Triple Angiokinase Inhibitor BIBF 1120 In Patients Suffering From Advanced Non-Small Cell Lung Cancer (NSCLC). Abstract # 163O. von Pawel. Proffered Papers 6 - Advanced NSCLC (parallel session)

(3) Hanna N et al. A Phase I study of continuous oral treatment with the triple angiokinase inhibitor BIBF 1120 together with pemetrexed in previously treated patients with NSCLC. Abstract P3-091. Presented at WCLC, 5 September 2007.

(4) Camidge R et al. A Phase I study of continuous oral treatment with the triple angiokinase inhibitor BIBF 1120 together with carboplatin and paclitaxel in patients with advanced NSCLC. Abstract P3-138. Presented at WCLC, 5 September 2007

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