Abstract CT031: Preliminary efficacy and safety results of savolitinib treating patients with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations
Authors: Lu Shun , Fang Jian , Cao Lejie , Li Xingya , Guo Qisen , Zhou Jianying , Cheng Ying , Jiang Liyan , Chen Yuan , Zhang Helong , Liang Zongan , Zhang Xin , Wu Biao , Shi Jianhua , Xu Hua , Huang Jianjin , Yang Zhixiong , Zeng Shan , Hu Yanping , Zhang Xiaodong , Wu Jingxun , Chen Gongyan , Yang Nong , Zhang Longzhen , Fu Yinjia , Li Jing , Wang Linfang , Ren Yongxin , Su Weiguo 
Published: August 2019

Abstract
Introduction: MET mutations have been linked with highly progressive clinical behaviors and poor prognosis in several tumor types. Savolitinib (also known as AZD6094, HMPL-504 and volitinib) is a novel, potent, highly selective MET inhibitor and investigated in solid tumors.
Methods: This is an open-label, single arm, multi-center phase II study to evaluate the efficacy and safety of savolitinib in MET exon 14 skipping mutant PSC or other types of NSCLC (NCT02897479). Eligible patients (pts) were diagnosed with unresectable or metastatic PSC or other types of NSCLC harboring MET exon 14 skipping mutations identified in tumor, plasma and/or pleural effusion. Mutations identified by local lab required to be confirmed by central lab test. Savolitinib 600mg was taken orally, once daily, until disease progression. The primary endpoint was objective response rate (ORR) per RECIST version 1.1. Here we report interim results after the first 34 enrolled pts.
Results: As of 17 December 2018, 315 pts were prescreened or confirmed by central lab, 49 identified/confirmed with MET exon 14 skipping mutations, and 34 treated (14 PSC; 20 other types of NSCLC). Median age was 69 years (range 54-85) and 68% pts were male. Prior antitumor drugs for advanced disease: 17 pts were treatment naïve, 13 pts received 1 regimen, and 4 pts ≥2 regimens. According to investigators’ assessment of 31 patients, 12 pts had confirmed partial responses (PR); 4 pts with newly reported, yet to be confirmed PRs; 10 had stable disease; 2 had disease progression; and 3 pts were efficacy non-evaluable due to early discontinuation. The remaining 3 pts had not been evaluated yet. Tumor histology for the confirmed PR pts was as follows: 6 with PSC, 5 adenocarcinoma, 1 adenosquamous carcinoma. Median treatment duration for the confirmed PR pts was 34+ weeks (range: 16-96+ weeks). Among all 34 pts, the most common (≥20%) drug-related treatment emergent adverse events (TEAEs) were nausea (41%), edema peripheral (38%), alanine aminotransferase increased (32%), aspartate aminotransferase increased (29%) and vomiting (21%). Overall, 12 (35%) pts had ≥ grade 3 related TEAEs, and 5 (15%) pts discontinued treatment due to related TEAEs. The most common related TEAE leading to treatment discontinuation was drug-induced liver toxicity (6%). Five pts have died on-treatment: 3 unrelated/unlikely related AEs, 1 probably related to treatment (tumor lysis syndrome), and 1 primary cause unknown.
Conclusion: Preliminary data suggested encouraging antitumor activity and an acceptable safety profile of savolitinib in pts with MET exon 14 mutated PSC or other types of NSCLC. Accrual of subjects in this study is ongoing.
Citation Format: Shun Lu, Jian Fang, Lejie Cao, Xingya Li, Qisen Guo, Jianying Zhou, Ying Cheng, Liyan Jiang, Yuan Chen, Helong Zhang, Zongan Liang, Xin Zhang, Biao Wu, Jianhua Shi, Hua Xu, Jianjin Huang, Zhixiong Yang, Shan Zeng, Yanping Hu, Xiaodong Zhang, Jingxun Wu, Gongyan Chen, Nong Yang, Longzhen Zhang, Yinjia Fu, Jing Li, Linfang Wang, Yongxin Ren, Weiguo Su. Preliminary efficacy and safety results of savolitinib treating patients with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT031.