Gene Therapy for Pleural Malignancies

Ad.hIFN-β (BG00001) is a replication-defective recombinant adenoviral vector containing the
human interferon-beta (hIFN-β) gene. This Phase I study is designed to evaluate the safety
and maximum tolerated dose (MTD) of two doses of intrapleural (IP) Ad.hIFN-β in subjects with
pleural malignancies either metastatic or pleural mesothelioma.

Five dose levels will be studied:

- Dose levels 1, 2, and 3 will be given on Days 1 and 15

- Dose levels 4 and 5 will be given on Days 1 and 8

Inclusion Criteria:

- must have malignant pleural effusion from mesothelioma or metastatic from primary
lung, breast, gastrointestinal, genitourinary, melanoma, or sarcoma

- must have evaluable disease

- must have ECOG performance status of 2

- must have pleural space involved with tumor accessible for pleural catheter

- must have FEV1 > 1 liter or 40% of predicted value

- must have completed radiotherapy and/or treatment with chemotherapy, cytotoxic, or
immunologic agents 4 weeks prior to dosing with BG00001

- concurrent Tarceva is allowed if patients has been on a stable dose for at least three
months and has not had serious adverse events

- patients on stable dose of hormone may continue use of hormone

- patients on stable dose of Tarceva for 3 months and without complications may remain
on Tarceva

Exclusion Criteria:

- malignant pleural effusions secondary to lymphoma

- rapidly re-accumulating, symptomatic malignant pleural effusions that require
immediate mechanical or chemical pleurodesis for palliation

- untreated brain metastases

- use of concurrent systemic steroids or immunosuppressants