PII-134 - PHARMACOKINETICS OF INFIGRATINIB AND ITS ACTIVE METABOLITES IN PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER OR GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA HARBORING FGFR2 GENE AMPLIFICATION

J. Yuan¹, L. Shen¹, T. Liu², H. Xu³, J. Yang⁴, J. Wei⁵, H. Jiang⁶, Y. Deng⁷, Y. Wang⁸, X. Zhang¹, J. Gong¹, C. Lyu⁹, L. Zhang⁹; ¹Peking University Cancer Hospital and Institute, ²Zhongshan Hospital Affiliated to Fudan University, ³Hubei Cancer Hospital, ⁴Fujian Cancer Provincial Cancer Hospital, ⁵Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, ⁶The First Affiliated Hospital of Zhejiang University School of Medicine, ⁷The Sixth Affiliated Hospital, Sun Yat-sen University, ⁸Shanxi Cancer Hospital, Taiyuan, ⁹Shanghai LianBio Development Co., Ltd..

Background: Fibroblast growth factor receptor (FGFR) 2 gene amplifications are found in 4.6% of patients with gastric cancer (GC) in China. Infigratinib is a selective ATP-competitive inhibitor of FGFR1–3 that has shown clinical activity in cancers with FGFR alterations. We report the pharmacokinetic (PK) profile of infigratinib and its active metabolites in patients with GC or gastroesophageal junction adenocarcinoma (GEJ) harboring FGFR2 gene amplifications.

Methods: In this phase 2, open-label, single-arm, multicenter study in China, patients with locally advanced or metastatic GC or GEJ harboring FGFR2 gene amplifications who had failed ≥2 lines of standard therapies or had exhausted available standard therapies were enrolled. Patients received infigratinib 125 mg orally once daily in a “3 weeks on, 1 week off” schedule for each 28-day cycle. As a secondary endpoint, PK parameters of infigratinib and its metabolites were calculated with a noncompartmental model from plasma concentrations after single and multiple doses of infigratinib. Accumulation ratio was evaluated using a mixed effects model based on the log-transformed PK parameters.

Results: As of 19 December 2022, 21 patients (19 GC and 2 GEJ) were included. After a single dose, peak infigratinib plasma concentration was reached at a median time of 3.0 (range: 2.0–24.0) hours, with mean Cmax (SD) of 98.1 (46.2) ng/mL and mean AUC0-inf (SD) of 806 (364) h*ng/mL; mean t1/2 (SD) was 6.2 (2.3) hours. The parent–metabolite ratio (SD) calculated from AUC0–t was 0.26 (0.13) for BHS697, 0.89 (0.40) for CQM157, and 0.08 (0.02) for BQR917. After 21-day dosing, a mean infigratinib Cmax,ss of 323 (186) ng/mL was reached at a median (range) of 4.0 (3.0–12.0) hours; mean AUCtau,ss was 4730 (2770) h*ng/mL. Accumulation ratio (geometric mean [90% CI]) based on AUCtau and Cmax was 6.0 [4.5–7.9] and 3.1 [2.2–4.2] for infigratinib, 6.1 [4.3–8.7] and 3.8 [2.7–5.4] for BHS697, 0.5 [0.3–0.6] and 0.4 [0.3–0.5] for CQM157, and 4.3 [3.2–5.8] and 2.6 [1.7–3.7] for BQR917, respectively.

Conclusion: The favorable PK profile of infigratinib in Chinese patients with GC or GEJ was consistent with profiles of infigratinib in patients with solid tumors. The findings support the use of the current regimen for further investigation of infigratinib in future GC or GEJ studies.