A Single Arm, Phase II Exploratory Clinical Study of Pemitinib in Advanced Gastric Cancer With Previous Standard Therapy Failure the FGFR Variant

Locally Advanced Unresectable Gastric Cancer

purpose of research： fundamental purpose: • To evaluate the effectiveness of pemitinib in patients with advanced gastric cancer who have failed standard therapy with fibroblast growth factor receptor 1-3 (FGFR1-3) variant (including but not limited to FGFR1-3 amplification, rearrangement / fusion, mutation, etc.). Secondary purpose: * To evaluate the safety and tolerability of pemitinib in patients with advanced gastric cancer who have previously failed standard therapy with the FGFR1-3 variant: including incidence of adverse events (AEs) and serious adverse events (SAEs) and association with therapy. Incidence of treatment-related AEs / SAEs. * Exploring efficacy and safety in subjects with different FGFR variant types. The end of the study: Main end point: • The primary endpoint of the study was the 6-month PFS rate (progression-free survival, defined as first dose to disease progression \[PD\] or death). Secondary end point: • Objective response rate (defined as the proportion of subjects achieving complete response (CR) or partial response (PR) by RECIST1.1 criteria). Duration of response (DOR, defined as the time from first CR or PR to PD, is used only for subjects with an objective response). * Disease control rate (DCR, defined as the proportion of subjects with CR + PR + stable disease stable \[SD\]). * Overall survival (OS, defined as the time of first dose to death from any cause). * Safety and tolerability: Grade evaluation for assessing the severity of adverse events according to NCI CTCAE (version 5.0), including: 1. Incidence, severity, and association of all AEs, TRAEs, SAEs, and the study drug; 2. Number and proportion of subjects stopping treatment due to the above adverse events; 3. Study changes in vital signs, physical examination findings, and laboratory results before, during and after treatment. * To describe the efficacy and safety in subjects with different FGFR gene variant types.

research design: This study is a prospective, single-arm, phase II clinical study. Patients with advanced gastric cancer who had failed standard treatment with FGFR1-3 variant, were included in the study by meeting the inclusion criteria after completing the informed consent. Patients will receive pemitinib 13.5 mg once daily (QD) orally on a 2-week dose / 1-week withdrawal regimen. Subjects will continue treatment until disease progression or intolerable toxicity. Clinical tumor imaging evaluation per RECIST v1.1, every 6 weeks (± 7 days) and every 9 weeks (± 7 days) after 48 weeks. Safety assessment was performed using NCI-CTCAE 5.0. Pemitinib, dose and mode of administration: Pemitinib will be treated as a 2 week / 1 week withdrawal regimen, 1 dose, 13.5mg, QD, 21 day cycle. Subjects should be on pometitinib at a fixed time per day to avoid inconsistent effects on plasma concentration. Sample size and statistical methods: 1. In this study, using the 6-month PFS rate as the primary endpoint, Calculted using the confidence interval method of Kapian-Meier estimation, Based on the historical data, The 6-month PFS rate of second-line chemotherapy in subjects with previous first-line treatment was approximately 20% (RAINBOW study, BRIGHTER Study), The 6-month PFS rate in subjects with previous second-line or more treatment was approximately 10% (Attraction-2 study), It is estimated that about 20% of the second-line and above treated subjects will be included in this study, The overall 6-month PFS rate was about 18%, Assuming that the 6-month PFS rate could be improved to 36%, Using the test level as one-sided α =0.1, ß=0.20, After follow-up for at least 6 months, With 80% confidence be observed with a 90% confidence interval lower bound greater than 18%, In total, 23 subjects will need to be enrolled. 2. Statistical analysis method: Continuous variables were described by mean, standard deviation, median, minimum and maximum values, and categorical variables were described by frequency and percentage. The proportion of subjects with the ORR and DCR and their 95% CI were estimated. Median PFS, DOR, and OS were estimated using Kaplan-Meier.

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