P86.09 A Single-Arm Phase II Study of Anlotinib Combined with Pemetrexed plus Cisplatin as a First-Line Therapy in Advanced NSCLC

Abstract

Patients with driver mutation-negative advanced NSCLC are mostly treated with platinum-based systemic therapy as the standard first-line therapy, but which achieves no satisfactory efficacy outcomes. Previous clinical studies exhibit that bevacizumab, an anti-VEGF inhibitor, plus chemotherapy improves survival for first-line treatment of advanced non-squamous NSCLC. Anlotinib, a novel oral multitarget tyrosine kinase inhibitor primarily targeting VEGFR2/3, FGFR1-4, PDGFRα/β and c-Kit, effectively inhibits angiogenesis and enhances tumor cell response to chemotherapy. The phase III ALTER 0303 trial showed anlotinib significantly improved progression-free survival (PFS) and overall survival (OS) in third-line or further treatment of advanced NSCLC. This open-label, single-arm, multicenter phase II study aims to explore whether anlotinib, as an oral multi-targeted antiangiogenic drug, in combination with pemetrexed plus cisplatin could further improve outcomes as first-line therapy for patients with non-driver mutation advanced non-squamous NSCLC. The single-arm, multicenter phase II study is ongoing and evaluating the efficacy and safety of anlotinib plus pemetrexed plus cisplatin for first-line treatment of driver mutation-negative advanced non-squamous NSCLC (NCT03671538). Patients aged 18 to 75 years and with histologically or cytologically confirmed locally advanced or metastatic stage IIIB/IV non-squamous NSCLC not harboring EGFR、ALK、ROS1 or BRAF genomic alterations are eligible in this study. Patients have to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and have received no previous systemic chemotherapy. Enrolled patients receive anlotinib (12 mg, QD, day 1 to 14 of a 21-day cycle) combined with pemetrexed (500 mg/m2, IV, day 1, 21 days per cycle) plus cisplatin (75 mg/m2, IV, day 1, 21 days per cycle). Those patients who have response or stable disease (SD) after 4-6 cycles of anlotinib in combination with pemetrexed plus cisplatin move to maintenance treatment with anlotinib alone (12 mg, QD, day 1 to 14 of a 21-day cycle) until disease progression or treatment intolerance. The primary endpoint is progression-free survival (PFS) according to RECIST v1.1. Secondary endpoints are 6-month and 12-month PFS rates, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Based on previous research results, we assume that the median PFS in patients with driver mutation-negative advanced non-squamous NSCLC treated by anlotinib plus pemetrexed plus cisplatin as first-line therapy is 7.5 months, then take an alpha value of 0.2 and a beta valve of 0.8. The follow-up time is 12 months. Finally, this study plans to enroll 62 patients calculated by NCSS & PASS 15.0 software and a one-sample Logrank test. Currently, 18 patients have been enrolled in the study (until June 26, 2020). Clinical trial in progress. Clinical trial in progress. Anlotinib, first-line therapy, driver mutation-negative