BTG's Plevitrexed Shows Promising Efficacy and Tolerability in a Phase I/II study

Data Published at Gastrointestinal Cancers Symposium

LONDON, England, Jan. 22, 2007: BTG plc (LSE: BGC), the medical innovations company, today announces the successful outcome of a Phase I/II study of plevitrexed, a selective inhibitor of thymidylate synthase targeting gastric, pancreatic and ovarian cancer. The study, presented at the ASCO 2007 Gastrointestinal Cancers Symposium1 in Orlando, Florida on 19 January, was designed to investigate the efficacy, safety and tolerability of plevitrexed in patients with advanced and/or metastatic gastric cancer.

Of the 28 patients who were evaluable for response at the recommended dose level of 130 mg/m2 taken into the Phase II part of the study, five patients had a partial response (17.9% response rate) and a further 15 patients (53.6%) had stable disease giving an overall disease control rate of 71.4%. One patient on the lower dose of 65 mg/m2 had a complete response and an additional five patients who received the higher dose of 165 mg/m2 had stable disease.

The use of nutritional supplements improved the dosing consistency and allowed for greater dose intensity. Only 30.6% of patients required dose interruptions or modifications compared with 61.8% of patients in a previous plevitrexed study2. The maximum tolerated dose doubled to 130 mg/m2 and was given more consistently than in the previous study and with fewer missed doses, but no increase in grade 3/4 neutropenia was observed.

The overall efficacy of plevitrexed was in line with other single agent therapy3,4 and with that seen in a previous study of plevitrexed5 (17% response rate), as well as with the recently reported two-drug combination treatment of cisplatin and 5-FU in the V325 comparative study6 (25% response rate for the cisplatin/5FU arm). The Progression Free Survival of 120 days for plevitrexed in the current study was similar to the Time To Progression of 111 days for cisplatin/5-FU in the V325 study, and median overall survival was also similar (239 days versus 258 days). The number of treatment cycles of cisplatin/5-FU was the same (4) but plevitrexed showed less toxicity, especially neutropenia (reduction in circulating white blood cells). In the V325 study the incidence of grade 3/4 neutropenia was 57% with 12% febrile neutropenia (with accompanying fever), compared with an incidence of 39% grade 3/4 neutropenia with only 3% febrile neutropenia in the current plevitrexed study.

Dr Anne Thomas, Senior Lecturer and Consultant in Medical Oncology at Leicester Royal Infirmary, a study investigator, commented: "With the promising single agent activity and side-effect profile shown in this study, plevitrexed represents an alternative, simple treatment option for patients who would not be able to tolerate the toxicity of multi-drug combinations."

Louise Makin, BTG's Chief Executive Office, added: "Based on the results of this and previous studies, we believe that plevitrexed is potentially an important new treatment option for people with advanced or metastatic gastric cancer. We are now seeking a partner to complete the clinical and commercial development of plevitrexed in this and other cancer types."

Study design

The study was an open label, non-comparative multi-centre Phase I/II trial in chemotherapy naïve patients with advanced and/or metastatic gastric cancer. Thirty patients were recruited to the Phase I part of the study designed to assess the safety and tolerability of different doses (65 mg/m2, 130 mg/m2 and 165 mg/m2) of plevitrexed (days 1 and 8 of a 3-week cycle) with nutritional levels of folic acid and vitamin B12 and to identify a dose for expansion into Phase II. In the Phase II part of the study, an additional 25 patients were added to give a total of 36 at the recommended dose level of 130 mg/m2, of whom 28 were evaluable for efficacy. Fifty-five patients who received at least one dose of plevitrexed were evaluable for toxicity.

The most common clinical adverse events reported were nausea (16 patients), fatigue (15 patients), vomiting (11 patients) and diarrhoea (11 patients). The most common grade 3/4 haematological events were neutropenia/leucopenia (21 patients including 3 cases of febrile neutropenia), thrombocytopenia (4 patients) and anaemia (12 patients).

References

1 Thomas A et al. A Phase I/II Study of Plevitrexed in the Treatment of Advanced Gastric Cancer. American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium (co-sponsors: AGA Institute, American Society for Therapeutic Radiology and Oncology, Society of Surgical Oncology, Inc.) 19-21 January 2007, Orlando, FL, USA, Abstract 79

2 Data on file

3 Ajani JA. Evolving Chemotherapy for Advanced Gastric Cancer. The Oncologist. 2005; 10: 49-58

4 Starling N and Cunningham D. New Treatments for Advanced Gastric Cancer. Oncology 2006, Touch Briefings, London. 2006; pp25-30

5 Petruzelka L. Phase II multicentre trial of ZD9331 monotherapy as first-line treatment for gastric cancer. Anti-Cancer Drugs. 2003; 14 (suppl 1): S7 - S12

6Van Cutsem E, Mioseyenko VM, et al. Phase III Study of Docetaxel and Cisplatin Plus Fluorouracil As First-Line Therapy for Advanced Gastric Cancer: A Report of the V325 Study Group. Journal of Clinical Oncology. 2006; 24: 4991-4997

About BTG

BTG in-licenses, develops and commercialises pharmaceuticals and other medical technologies. With a substantial and growing revenue stream of royalties and milestone payments from out-licensed products, BTG continues to strengthen its pipeline of preclinical and clinical development programmes. Active in the fields of oncology, diseases of ageing, neuroscience, drug repositioning and medical devices, BTG works from its offices in London, Philadelphia and Osaka with a global partner network of healthcare companies and research organisations. For further information, visit: www.btgplc.com <http://www.btgplc.com/> .

For further information contact:

BTG

Andy Burrows, Director of Investor Relations

+44 (0)20 7575 1741

Christine Soden, Chief Financial Officer

+44 (0)20 7575 1591

De Facto Communications

Maria Patey

+44 (0)20 7861 3838

Financial Dynamics

Ben Atwell / Anna Keeble

+44 (0)20 7831 3113

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Posted: January 2007

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