Ensartinib, Carboplatin, Pemetrexed and Bevacizumab for the Treatment of Stage IIIC or IV or Recurrent ALK-Positive Non-small Cell Lung Cancer

Description

PRIMARY OBJECTIVES:

I. To determine the safety of ensartinib in combination with carboplatin, pemetrexed and bevacizumab in patients with ALK-rearranged advanced non-small cell lung cancer (NSCLC).

II. Determine the recommended phase 2 dose (RP2D) of ensartinib in combination with carboplatin, pemetrexed and bevacizumab.

SECONDARY OBJECTIVES:

I. To determine an objective response rate (ORR) in patients with ALK-rearranged advanced NSCLC treated with ensartinib in combination with carboplatin, pemetrexed and bevacizumab using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

II. To determine progression-free survival (PFS). III. To determine overall survival.

EXPLORATORY OBJECTIVE:

I. To determine biomarkers associated with response and resistance to the study combination.

OUTLINE: This is a dose de-escalation study of ensartinib and fixed-dose carboplatin, pemetrexed, and bevacizumab followed by a dose-expansion study.

INDUCTION THERAPY: Patients receive ensartinib orally (PO) once daily (QD) on days 1-21, carboplatin intravenously (IV) over 15-60 minutes on day 1, pemetrexed IV over 10 minutes on day 1 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive ensartinib PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.