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Ref Type | Journal Article | ||||||||||||
PMID | (28589492) | ||||||||||||
Authors | Michael M, Bang YJ, Park YS, Kang YK, Kim TM, Hamid O, Thornton D, Tate SC, Raddad E, Tie J | ||||||||||||
Title | A Phase 1 Study of LY2874455, an Oral Selective pan-FGFR Inhibitor, in Patients with Advanced Cancer. | ||||||||||||
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Abstract Text | We report here a phase 1 study of LY2874455, a potent oral selective pan-fibroblast growth factor receptor (FGFR) inhibitor.The primary objective was to determine the recommended phase 2 dosing (RP2D). Secondary objectives included determining toxicity, antitumor activity, pharmacokinetics (PK), and pharmacodynamic (PD) properties of LY2874455.This study comprised two parts: (a) dose escalation with 3 + 3 cohorts in patients with solid tumors and (b) dose-expansion cohorts in patients with gastric cancer (GC) and non-small cell lung cancer (NSCLC). Part A: 36 patients in 11 dose cohorts ranging from 2 to 24 mg twice daily (BID). RP2D was 16 mg BID. Part B: GC cohort, 29 patients, NSCLC cohort, 27 patients, all treated at the RP2D.LY2874455 was slowly absorbed and generally showed linear PK. The effective half-life was ∼12 h. PD properties of LY2874455 occurred at doses ≥10 mg by increases in serum phosphorus. Phosphate binders were administered to control serum phosphorus. LY2874455 was generally well tolerated; most toxicities were grade 1 or 2; most frequent were hyperphosphatemia, diarrhea, and stomatitis.part A: 24 patients evaluable: 1 patient in the 14-mg BID cohort with GC had a partial response (PR); 14 patients had stable disease (SD); part B: NSCLC cohort: 11 of 12 evaluable patients had SD; GC cohort: 15 patients evaluable: 1 patient with PR; 12 patients with SD.LY2874455 has an RP2D of 16 mg BID and demonstrated good tolerability and activity in solid-organ cancer patients. The role of FGFR inhibition on tumor growth in patients requires further study. (NCT01212107). |
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