Background: Apatinib, a highly selective small-molecule tyrosinase inhibitor of VEGFR2, is the third-line standard therapy for patients (pts) with advanced gastric cancer. Many previous studies have preliminarily demonstrated the efficacy and safety of apatinib combined with chemotherapy in the second-line treatment of gastric cancer. Comparing with pts who have not undergone surgery, previous pharmacological study has found that pts who have undergone gastric cancer surgery have lower bioavailability and can tolerate higher doses of apatinib (Clin Pharmacokinet. 2017 Jan; 56(1):65-76). However, there is no prospective evidence of apatinib plus chemotherapy for second line treatment in pts with postoperatively gastric cancer. Methods: To explore the efficacy, safety and the maximum tolerated dose (MTD) of apatinib from apatinib+chemotherapy for second line treatment in pts with postoperatively gastric cancer. We designed ACHIEVE as a multicenter, dose-escalation, and dose-expansion trial in pts with gastric or gastroesophageal junction cancer who had prior undergone gastrectomy. In part 1 (dose escalation), pts who had received previously first-line treatment will be assigned to 1 of 3 three dose groups: (1) apatinib (250mg qd) + chemotherapy drug; (2) apatinib (500mg qd) + chemotherapy drug; (3) apatinib (750mg qd) + chemotherapy drug. The therapeutic drugs for second-line chemotherapy are determined by the investigator, it’s recommended to use docetaxel or albumin-bound paclitaxel, and chemotherapeutics are used for up to 6 cycles. In part 2 (dose expansion), pts will be treated with apatinib (MTD determined by dose escalation, qd) + chemotherapy drug. Whether PD-1 or PD-L1 inhibitors have been used in the first-line treatment will be analyzed as a subgroup analysis factor. Primary endpoints are progression-free survival (PFS) and MTD. Secondary endpoints include confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety. AEs will be monitored throughout the study and graded per NCI CTCAE v5.0. Tumor response will be assessed by RECIST v1.1 every 6 weeks in the first 18 weeks, and every 9 weeks thereafter. Clinical trial information: ChiCTR2100048288.