Combination of Docetaxel Plus Savolitinib in Refractory Cancer Patients: A Report on Phase I Trial

Seung Tae Kim, Sujin Lee, Minhwa Park, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Young Suk Park, Won Ki Kang, Esha A. Gangolli, Hyeongchan Shin, Kyoung Mee Kim, Simon J. Hollingsworth, Peter G.S. Mortimer, Jeeyun Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

MET amplification is a frequently observed genomic aberration in solid tumors. We conducted a phase I trial to evaluate dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) for the combination therapy. The following dose levels were tested in this single-arm phase I study: docetaxel as an intravenous infusion over 1 hour at 60 mg/m 2 once every 3 weeks of a 21-day schedule plus savolitinib (level 1, 200 mg qd; level 2, 400 mg qd; level 3, 600 mg qd; level 4800 mg qd). In total, there were 17 patients enrolled on to this study [7 gastric cancer (GC) patients, 5 melanoma patients, 3 sarcoma patients, and 2 rectal cancer patients]. Most of the patients (14 of 17) were heavily pretreated (≥third line or greater lines of treatment). For the first 3 cohorts (200 mg savolitinib + docetaxel 60 mg/m 2 , 400 mg savolitinib + docetaxel 60 mg/m 2 , 600 mg savolitinib + docetaxel 60 mg/m 2 ), there were no DLTs. In the fourth dose cohort (800 mg savolitinib + docetaxel 60 mg/m 2 ), one DLT occurred with generalized edema grade 3 that required intensive management. One GC patient with both MET overexpression (3+) and MET amplification (MET/CEP7 ratio, 7.3) achieved a durable partial response for 297 days, and another MET-amplified GC patient (MET/CEP7 ratio, 7.6) achieved stable disease for 86 days. Due to the higher incidence of G4 neutropenia in cohort 4 (800 mg), we recommend savolitinib 600 mg qd in combination with docetaxel 60 mg/m 2 as the RP2D for phase II trial. The combination therapy demonstrated a very promising antitumor activity with durable responses in MET amplified GC patients.

Original languageEnglish
Pages (from-to)597-601
Number of pages5
JournalTranslational Oncology
Volume12
Issue number4
DOIs
StatePublished - Apr 2019

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