Abstract C121: A non-randomized, open-label, single-arm, phase 2 study of LY2875358 in Asian patients with MET diagnostic positive, advanced gastric cancer
Authors: Chung Hyun Cheol , Satoh Taroh , Oh Do-Youn , Park Se Hoon , Kadowaki Shigenori , Wacheck Volker , Yamamura Ayuko , Uenaka Kazunori , Wang Xuejing Aimee , Wijayawardana Sameera R. , Doi Toshihiko 
Published: May 2016

Abstract
Introduction: MET is expressed in gastric cancer and associated with poor clinical outcome. LY2875358 (LY) is a humanized immunoglobin G4 (IgG4) monoclonal bivalent antibody blocking ligand-dependent and independent MET signaling. In preclinical studies, LY showed single agent anti-tumor activity for MET amplified gastric cancer in xenograft models. Based on these results, a non-randomized, multicenter, single-arm, open-label, Phase 2 study was conducted to evaluate the antitumor activity of LY in patients (pts) with MET diagnostic positive (+), advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Methods: Pts with MET diagnostic (+), advanced gastric or GEJ adenocarcinoma, who had received 2 prior chemotherapies, were administered LY 2000 mg as flat dose intravenously every 2 weeks (Q2W) on a 28 day cycle. MET diagnostic (+) tumor status was determined by immunohistochemistry (IHC). The primary objective was to evaluate the activity of LY in terms of progression-free survival (PFS) rate at 8 weeks (+ 3 days). Secondary objectives were to assess other efficacy variables (eg overall response rate, disease control rate [DCR], PFS, overall survival [OS]), toxicity and safety profile of LY, and pharmacokinetics (PK). The exploratory objectives included evaluation of pharmacodynamics, pharmacogenomics, and exploratory biomarkers.
Results: Tumor samples of 65 pts were screened for MET expression by IHC and 15 pts (23.1%) with MET diagnostic (+) were enrolled in this study. Fifteen pts (5 female, 10 male) from Asia (Japan 8, Korea 7) with a median age of 63 years (range 39-74) were enrolled. PFS rate at 8 weeks was 47% (70% Confidence Interval [CI]: 33%, 59%). There was no partial response according to RECIST, while shrinkage of tumor size was observed in 3 out of 15 pts. DCR was 40.0%, with stable disease shown in 6 out of 15 pts. Median PFS was 8.3 weeks (95% CI: 4.1, 12.1) with stable disease for up to a maximum of 37.1 weeks. Median OS was 17.1 weeks (95% CI: 6.3, Not Available). A total of 12 pts (80%) experienced at least 1 LY-related treatment-emergent adverse event (TEAE). Common LY-related TEAE (all grades) included constipation and hypoalbuminemia (3 pts [20%] each). LY-related TEAEs with Grade ≥ 3 were hyponatremia and hyperuricemia (2 events in 1 patient), and hyperkalemia (1 patient). Serious adverse events were reported in 6 patients, none of which was related to LY. There was no TEAE leading to death or study treatment discontinuation. PK profiles were similar to those observed in previous studies of LY monotherapy, which were conducted in the United States, and the majority of patients were Caucasian. Exploratory biomarker analysis (IHC data) will be presented at the venue.
Conclusion: LY 2000 mg Q2W showed a well-tolerated safety profile with a limited single agent activity in heavily pretreated patients with MET diagnostic (+), advanced gastric or GEJ adenocarcinoma.
Citation Format: Hyun Cheol Chung, Taroh Satoh, Do-Youn Oh, Se Hoon Park, Shigenori Kadowaki, Volker Wacheck, Ayuko Yamamura, Kazunori Uenaka, Xuejing Aimee Wang, Sameera R. Wijayawardana, Toshihiko Doi. A non-randomized, open-label, single-arm, phase 2 study of LY2875358 in Asian patients with MET diagnostic positive, advanced gastric cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C121.