| Title | A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients withEGFR-mutated,MET-amplified advanced non-small-cell lung cancer |
| Authors | Yang, Jin-Ji Fang, Jian Shu, Yong-Qian Chang, Jian-Hua Chen, Gong-Yan He, Jian Xing Li, Wei Liu, Xiao-Qing Yang, Nong Zhou, Caicun Huang, Jian An Frigault, Melanie M. Hartmaier, Ryan Ahmed, Ghada F. Egile, Coumaran Morgan, Shethah Verheijen, Remy B. Mellemgaard, Anders Yang, Liu Wu, Yi-Long |
| Affiliation | Guangdong Prov Peoples Hosp, Guangdong Lung Canc Inst, 106 Zhongshan Er Rd, Guangzhou 510080, Peoples R China Guangdong Acad Med Sci, 106 Zhongshan Er Rd, Guangzhou 510080, Peoples R China Beijing Canc Hosp, Beijing, Peoples R China Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing, Peoples R China Fudan Univ, Canc Hosp, Shanghai, Peoples R China Harbin Med Univ, Canc Hosp, Harbin, Peoples R China Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China Jilin Univ, Hosp 1, Changchun, Peoples R China Chinese Peoples Liberat Army, Hosp 307, Beijing, Peoples R China Hunan Canc Hosp, Changsha, Peoples R China Shanghai Pulm Hosp, Shanghai, Peoples R China Soochow Univ, Affiliated Hosp 1, Suzhou, Jiangsu, Peoples R China AstraZeneca, Translat Med, Oncol R&D, Boston, MA USA AstraZeneca, Clin Pharmacol & Safety Sci, BioPharmaceut R&D, Cambridge, England AstraZeneca, R&D Oncol, Precis Med, Cambridge, England AstraZeneca, Late Phase Oncol R&D, Cambridge, England AstraZeneca, Late Phase Oncol R&D, Cambridge, England AstraZeneca, Global Med Dev, Oncol, Shanghai, Peoples R China |
| Keywords | ACQUIRED-RESISTANCE OPEN-LABEL INHIBITOR MUTATION GROWTH NSCLC ADENOCARCINOMA MULTICENTER PROGRESSION DISCOVERY |
| Issue Date | Apr-2021 |
| Publisher | INVESTIGATIONAL NEW DRUGS |
| Abstract | Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended first-line treatments in EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC). However, acquired resistance (e.g. MET amplification) is frequently observed. Savolitinib (volitinib, HMPL-504, AZD6094) is an oral, potent, and highly selective MET-TKI. In this phase Ib, open-label, multicenter study, we enrolled Chinese patients with EGFRm advanced NSCLC, whose disease progressed following prior EGFR-TKI treatment. In the safety run-in, patients received savolitinib 600 or 800 mg plus gefitinib 250 mg orally once daily, and dose-limiting toxicities were recorded. In the expansion phase, patients with MET amplification received savolitinib plus gefitinib. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity. Thirteen patients were enrolled in the safety phase (median age 52 years, 46% female) and 51 enrolled in the expansion phase (median age 61 years, 67% female). No dose-limiting toxicities were reported in either dose group during the safety run-in. Adverse events of grade >= 3 in the safety run-in and expansion phases (n = 57) were reported in 21 (37%) patients. The most frequently reported adverse events (all grades) were: vomiting (n = 26, 46%), nausea (n = 23, 40%), increased aspartate aminotransferase (n = 22, 39%). Of four deaths, none were treatment-related. The objective response rates in EGFR T790M-negative, -positive, and -unknown patients were 52% (12/23), 9% (2/23), and 40% (2/5), respectively. Savolitinib 600 mg plus gefitinib 250 mg once daily had an acceptable safety profile and demonstrated promising antitumor activity in EGFRm, MET-amplified advanced NSCLC patients who had disease progression on EGFR-TKIs. NCT02374645, Date of registration: March 2nd 2015. |
| URI | http://hdl.handle.net/20.500.11897/621633 |
| ISSN | 0167-6997 |
| DOI | 10.1007/s10637-020-01010-4 |
| Indexed | SCI(E) |
| Appears in Collections: | 待认领 |
