Alpelisib and Paclitaxel in PIK3CA-altered Gastric Cancer

Summary

Alpelisib (BYL719) is a PIK3CA-specific inhibitor, which was developed by Novartis (Basel, Switzerland). Our group conducted pre-clinical study of alpelisib in eight gastric cancer cell lines: four PIK3CA wild-type (SNU638, SNU668, SNU1, and SNU16) and four PIK3CA mutant (SNU719, AGS, SNU601, and MKN). As a result, alpelisib preferentially inhibited the growth of gastric cancer cells with PIK3CA mutations. In addition, alpelisib inhibited cell growth via G1 arrest and subsequently induces apoptosis in GC cells, and this effect is more remarkable in cells harboring PIK3CA mutations. Moreover, alpelisib in combination with paclitaxel showed synergistic cytotoxic effects and significantly increased apoptosis compared with alpelisib or paclitaxel monotherapy in GC cells. The purpose of the study is to define the maximal tolerated dose (MTD) and recommended phase II dose (RP2D) of paclitaxel and alpelisib combination therapy in patients with advanced tumors and to evaluate the efficacy of paclitaxel and AZD8186 combination therapy as a second-line therapy in patients with advanced gastric cancer with PTEN aberrations. This study is divided into Phase IB and Phase II.

Timeline

Start

2020-09-01

Primary completion

2023-06

Completion

2024-12

Drugs

Indications