A first-in-human dose phase 1 study of LY3009120 in advanced cancer patients.

• DOI: 10.1200/jco.2017.35.15_suppl.2507
• Publication Date: 2018-09-06T15:41:11Z
• Authors: David S. Hong; Antoine Hollebecque; Michael S. Gordon; Keith T. Flaherty; Geoffrey Shapiro; Jordi Rodon; Michael Millward; Nina Ramdas; Wei Zhang; Ling Gao; Amanda Sykes; Melinda D. Willard; Danni Yu; Andrew Schade; Daniel Lee Flynn; Michael Kaufman; Sheng-Bin Peng; Ilaria Conti; Ramon Velasquez Tiu; Ryan J. Sullivan
• Keywords: Tolerability; Pharmacodynamics

2507 Background: LY3009120, a pan-Raf and dimer inhibitor, demonstrates inhibition of phospho-Mek/Erk tumor growth in several non-clinical cancer models with BRAF, NRAS, or KRAS mutations. This is the first-in-human phase 1 study LY3009120 patients (pts) advanced cancer. Methods: The safety tolerability was evaluated pts aged 18 years older who had an ECOG performance status ≤1, at least unidimensionally measurable lesion (RECIST 1.1), adequate organ function (NCT02014116; I6X-MC-JBDA; Eli Lilly & Co.). sought to determine recommended 2 dose using toxicity band method safety, pharmacokinetic, preliminary efficacy LY3009120. Pharmacodynamic (PD) biomarkers, including pERK, p27 Ki67, were tissue. escalation dosages from 50 mg 500 by mouth twice daily cancers. Results: 34 (3 mg, 4 100 3 200 15 300 7 400 mg) pt expansion (1 received one January 2, 2016 (median age = 47.4 yrs, range: 26-82 ). Most gene mutation (BRAF, n 7; N/KRAS, 18); most common types included colon (n 9), non–small cell lung 8), pancreatic 5). There 6 dose-limiting toxicities phase: (G3 dermatitis acneiform [n 1] G2 blurred vision 1]); (G2 increased ALT G3 hyperbilirubinemia mg: arthralgia/myalgia stomatitis/pain 1]). Based on these data, maximum tolerated for determined be daily. Treatment-emergent adverse events related occurring ≥10% fatigue (34%), nausea (31%), decreased appetite (20%), (20%) (Grade 1,2). A proportional increase exposure observed, but not dose. best response stable disease 5 pts. PD effect rtPCR observed tested paired samples. Conclusions: well doses Updated data will presented meeting. Clinical trial information: NCT02014116.