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A phase I clinical trial was conducted to evaluate the anticancer activity and maximum tolerated dose (MTD) of apatinib plus POF in treatment\u2010na\u00efve patients with AGC and to establish a recommended phase II dose. Participants received escalating doses of daily oral apatinib (250, 375, 500, 625, 750, and 850\u2009mg) plus POF every 2\u2009weeks using a conventional \u201c3\u2009+\u20093\u201d study design. Among 21 treated patients, one experienced a dose\u2010limiting toxicity (grade 3 skin ulceration at 850\u2009mg). No MTD was reached. Apatinib 750\u2009mg plus POF was recommended for phase II study. The most common grade 3\u20134 adverse events (AEs) were neutropenia (33.3%), mucositis (14.3%), and hand\u2010foot syndrome (14.3%). Median progression\u2010free and overall survival were 10.4\u2009months (95% CI: 6.3, 14.6) and 18.4\u2009months (95% CI: 9.8, 28.2), respectively. Apatinib up to 850\u2009mg coadministered with POF was well tolerated with manageable AEs. 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