A Phase 1b/2 Study in Asian Subjects With Non-Small Cell Lung Cancer

A Phase 1b/2 Study of AV-299 (Formerly SCH 900105) in Combination With Gefitinib in Asian Subjects With Non-Small Cell Lung Cancer (P06162)

During Phase 1b portion, there will be a dose-escalation of AV-299 (formerly SCH 900105) in combination with the recommended dose of gefitinib in subjects with NSCLC or advanced solid tumor. The objective is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended Phase 2 dose (RP2D) in combination with gefitinib for the Phase 2 portion.

The Phase 2 is an open-label, 2-arm, randomized study designed to compare the combination of AV-299 (formerly SCH900105) and gefitinib versus gefitinib alone in clinically selected Asian subjects with previously untreated lung adenocarcinoma who have a high likelihood of harboring activating EGFR mutations. Subjects who progress after initial disease control in the gefitinib alone arm may crossover to the combination arm.

Inclusion Criteria:

• Asian ethnicity.
• ECOG performance status of 0-2.
• Phase 1b (only): Diagnosis of one of the following unresectable NSCLC with or without prior therapy advanced solid tumor that progressed after standard therapy
• Phase 2 only: Histologic or cytologic confirmation of unresectable locally advanced or metastatic stage IIIB/IV lung adenocarcinoma with at least one measurable lesion, per Response Evaluation Criteria in Solid Tumors (RECIST-Version 1.1).
• Phase 2 only: Never smoker or light ex-smoker.
• Available tumor tissue for determination of EGFR mutational status and immunohistochemistry analysis
• Adequate hematologic, hepatic, renal and coagulation function
• No active central nervous system metastases
• Prior radiotherapy is allowed if 14 days from first dose of study drug and toxicity is resolved; additionally in Phase 2 only, ≥1 target lesion not irradiated or with definitive progression after prior radiation therapy.
• Agreement to use effective contraception.
• Phase 2 only: Subjects on Gefitinib monotherapy arm must have documented CR, PR, or SD for ≥12 weeks prior to disease progression in order to cross over to combination therapy arm.

Exclusion Criteria:

• Phase 2 only: Prior chemotherapy or prior treatment with epidermal growth factor receptor (EGFR) inhibitor, including both tyrosine kinase inhibitors and monoclonal antibodies. There is no limit to the number of therapies for subject being considered for Phase 1b.
• History of neoplasm other than the entry diagnosis.
• Pregnancy or lactation.
• Myocardial infarction within 6 months prior to initiation of study treatment.
• A serious active infection.
• Known human immunodeficiency virus infection.
• A serious underlying medical condition that would impair the ability of the subject to receive protocol treatment.
• A major surgical procedure, open biopsy, or significant traumatic injury.
• Thrombotic or embolic events.
• Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.
• Any condition that impairs absorption of oral agents or the subject's ability to swallow whole pills.
• Diarrhea ≥ Grade 2 or active Inflammatory Bowel Disease.
• Severe acute or chronic medical, psychiatric, or behavioral condition or laboratory abnormality.
• Diagnosis of interstitial lung disease.
• Any medications or treatments prohibited by the protocol.