Study of NOV-002 in Combination With Chemotherapy to Treat Lung Cancer

Phase 3 Trial, Randomized, Open-Label, of NOV-002 in Combination With Paclitaxel and Carboplatin vs. Paclitaxel and Carboplatin Alone for the Treatment of Advanced Non-Small-Cell Lung Cancer (NSCLC)

The purpose of this clinical trial is to find out whether or not the combination of NOV-002 with chemotherapy (paclitaxel and carboplatin) is better at improving overall survival time when compared to chemotherapy alone in people with non-small cell lung cancer (NSCLC).

Earlier clinical trials in NSCLC showed that patients treated with NOV-002 in combination with chemotherapy had a better response (their tumors got smaller in one United States Phase 1/2 trial) than patients who received chemotherapy alone; and in two Phase 2 trials done in Russian patients, at the end of one year, patients treated with NOV-002 with chemotherapy had a better survival rate than patients who did not receive NOV-002 with their chemotherapy.

NSCLC is a widespread disease with extremely high mortality and morbidity. Even the most widely accepted standard of care chemotherapy in advanced NSCLC, platinum-based doublets, are only palliative, providing marginal efficacy as measured by survival. In addition, such chemotherapy is accompanied by severe, sometimes life-threatening, toxicities which often limit its application. Thus, there is a clear need for new, more effective and safer therapies for advanced NSCLC. In Phase 2 trials, NOV-002 demonstrated a higher response rate and improved survival compared to chemotherapy alone in patients with advanced NSCLC, and was well-tolerated in this patient group. Thus, we are conducting a large Phase 3 trial of NOV-002 to better define its clinical profile and potential benefit in advanced NSCLC patients.

The overall design of this Phase 3 trial reflects major elements of the previous Russian and US clinical trials in advanced NSCLC - it is an open label, randomized controlled trial comparing NOV-002 in combination with first-line chemotherapy (paclitaxel + carboplatin) to first-line chemotherapy alone. Furthermore, it is designed and powered to be a pivotal, registrational trial, sufficient for approval. As its primary efficacy endpoint, this Phase 3 trial aims to demonstrate that the combination of NOV-002 with paclitaxel and carboplatin results in improved overall survival when compared with paclitaxel and carboplatin alone. In addition, several secondary efficacy endpoints will be assessed, including progression free survival, tumor response rate and duration of response, quality of life, myelosuppression and immunomodulation. Overall survival was chosen as the primary endpoint of this trial in the context of FDA (Draft) Guidance ("Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics", April 2005). This Guidance indicates that an improvement in overall survival should be evaluated in randomized controlled trials and is of unquestioned clinical benefit. It indicates that the endpoint is precise and easy to measure, documented by the date of death, and states that bias is not a factor in endpoint measurement, and blinding is not essential. This Phase 3 randomized, controlled, open-label trial thus conforms to this Guidance.

Inclusion Criteria:

• Diagnosis of Stage IIIb with malignant pleural or pericardial effusion or Stage IV (American Joint Committee on Cancer [AJCC]) NSCLC
• ECOG performance score of 0 or 1
• Adequate bone marrow, hepatic, and renal function
• New York Heart Association (NYHA) score 1-2
• Life expectancy of at least 12 weeks
• Women of child-bearing potential and men whose partners are of child-bearing potential must be willing to use an acceptable method of birth control during trial participation or are surgically sterile or women who are post-menopausal (defined as not having a menstrual cycle for greater than two years).
• The patient or patient's legal representative has the ability to understand the requirements of the trial, has provided written informed consent, and agrees to abide by the trial restrictions and to return for the required assessments.
• The patient must be able to self administer daily subcutaneous injections or his/her caregiver must be able to administer daily subcutaneous injections.

Exclusion Criteria:

• Prior chemotherapy for advanced NSCLC or the patient has received prior neoadjuvant or adjuvant chemotherapy for NSCLC in the year prior to the date of randomization
• Patients with central nervous system (CNS) metastases
• Any systemic disease precluding chemotherapy
• Chronic use of systemic corticosteroids in pharmacological doses
• Known or history of HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Contraindication to treatment with paclitaxel or carboplatin or any of the components of NOV-002
• Any known preexisting medical condition, including substance abuse, that could interfere with the patient's participation in and completion of the protocol
• Have received any investigational drug, defined as a drug for which there is no Food and Drug Administration (FDA) approved indication, within the 30 days prior to randomization
• Pregnant female or nursing mother