810P - Phase I study of apatinib combined with POF (paclitaxel plus FOLFOX) in patients (pts) with treatment-naïve advanced gastric cancer (TNAGC)

Abstract

BackgroundApatinib, is a novel, small molecule, selective VEGFR-2 TKI and is approved in China as third-line treatment for patients with AGC. Preclinical and clinical data suggests that apatinib may enhance the chemotherapeutic drugs cytotoxicity by inhibiting cell membrane–bound ATP-binding cassette transporters.POF is effective in pts with TNAGC reported in our phase II study. We evaluated the safety and efficacy of apatinib plus POF in TNAGC. MethodsThis was a phase I single center study with standard 3+3 design for pts with TNAGC. The primary endpoints are determining dose limiting toxicities (DLT) and maximum tolerated dose (MTD). Secondary endpoints include overall survival (OS), progression free survival (PFS), response rate (RR), and quality of life (QOL). Initial plan was to enroll pts in 5 escalating dose levels of apatinib (250/375/500/625/750mg daily) plus POF, consisted of paclitaxel 135mg/m2, followed by mFOLFOX6 omitted 5-Fu bolus, every 14 days repeated. Eligible pts had ECOG PS 0-1, age 18-70, and adequate organ function. DLT was any treatment-related hematologic ≥ grade 4 toxicity (except for neutropenia lasting for ≤ 5 days), or non-hematologic ≥ grade 3 toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase). Results17 pts were treated in 5 different dl of apatinib plus POF (3 in each dl, except for 5 in dl 625mg). Median age was 55 years (range 25-69) with 76.5% male. All pts were evaluated for toxicity, but only 15 were evaluable for DLT. 2 pts in dl 625mg were replaced as they came off of study within 28 days (1 due to poor adherence to take apatinib as prescribed, 1 due to concealing his prior chemotherapy). Zero DLTs were observed at all dl. Only 3 pts had grade 3 neutropenia. The rest of toxicities were ≤ grade 2. Most frequent of toxicity were anemia (64.71%), hypoalbuminemia (58.82%), and neutropenia (47.06%). 11 pts were evaluable for response (8 PR [72.73%], 1 SD, 2 PD).5 pts have been on treatment > 6 months. ConclusionsApatinib can be safely administered up to 750mg daily combined with POF for pts with TNAGC.Phase II will begin after phase I completion and will evaluate efficacy of apatinib 750mg plus POF. Clinical trial identificationNCT03244774; Release date: August 10, 2017. Legal entity responsible for the studyRongbo Lin. FundingJiangsu HengRui Medicine Co., Ltd. DisclosureAll authors have declared no conflicts of interest.