Savolitinib ± Osimertinib in Japanese Patients with Advanced Solid Malignancies or EGFRm NSCLC: Ph1b TATTON Part C.
Abstract | BACKGROUND: OBJECTIVE: PATIENTS AND METHODS: In Part C of the phase Ib, multi-arm, open-label, multicenter TATTON study, two cohorts of Japanese adult patients were evaluated across six study centers in Japan. Patients with advanced solid malignancies received oral savolitinib monotherapy 400 mg once daily (qd), escalating to 600 mg; patients with advanced EGFR mutation-positive (EGFRm) non-small-cell lung carcinoma (NSCLC) who progressed on prior EGFR-TKI received oral osimertinib 80 mg+savolitinib 300/400/600 mg qd combination therapy. Primary endpoints: safety/tolerability of savolitinib±osimertinib, and maximum tolerated dose(s) (MTD) definition. RESULTS: Seventeen patients received monotherapy; 12 received combination. Dose-limiting toxicities (DLTs): with monotherapy, 400 mg, none reported; 600 mg, n = 3/9 evaluable patients (33%) reported DLTs (grade 3 and 4 alanine aminotransferase and aspartate transaminase increased, and grade 4 drug-induced liver injury). With combination: 400 mg, 1/6 (17%) reported DLTs (grade 2 fatigue, nausea, and myalgia); 300 mg, none reported; 600 mg, 3/4 (75%) reported DLTs (grade 2 pyrexia, grade 3 skin reaction, and anaphylactic shock). Grade ≥3 adverse events were reported in 41% of patients receiving monotherapy and 33% receiving combination. TATTON is no longer recruiting patients. CONCLUSIONS: TRIAL REGISTRATION: Clinicaltrials.gov; NCT02143466; 21 May 2014.
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Authors | Kiyotaka Yoh, Tomonori Hirashima, Hideo Saka, Takayasu Kurata, Yuichiro Ohe, Toyoaki Hida, Anders Mellemgaard, Remy B Verheijen, Xiaoling Ou, Ghada F Ahmed, Manabu Hayama, Ko Sugibayashi, Geoffrey R Oxnard |
Journal | Targeted oncology
(Target Oncol)
Vol. 16
Issue 3
Pg. 339-355
(05 2021)
ISSN: 1776-260X [Electronic] France |
PMID | 33939068
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Intramural)
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Chemical References |
- Acrylamides
- Aniline Compounds
- Pyrazines
- Triazines
- 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine
- osimertinib
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Topics |
- Acrylamides
(pharmacology, therapeutic use)
- Aged
- Aniline Compounds
(pharmacology, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology, therapeutic use)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, pathology)
- Humans
- Japan
- Lung Neoplasms
(drug therapy, pathology)
- Male
- Middle Aged
- Pyrazines
(pharmacology, therapeutic use)
- Triazines
(pharmacology, therapeutic use)
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