Phase 1b study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma
Year: 2015
Type: article
Study design: Clinical Trial
Abstract: // David S. Hong 1 , Razelle Kurzrock 1 , Gerald S. Falchook 2 , Corina Andresen 3 , Jennifer Kwak 3 , Min Ren 4 , Lucy Xu 4 , Goldy C. George 1 , Kevin B. Kim 1 , Ly M. Nguyen 1 , James P. O’Brien 3 , John Nemunaitis 5 1 The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Sarah Cannon Research Institute at HealthONE, Denver, CO, USA 3 Former employees of Eisai Inc., Woodcliff Lake, NJ, USA 4 Eisai Inc., Oncology, Woodcliff Lake, NJ, USA 5 Mary Crowley Cancer Research Center, Dallas, TX, USA Correspondence to: David S. Hong, e-mail: [email protected] Keywords: lenvatinib, melanoma, pharmacodynamic, phase 1b, advanced solid tumors Received: July 15, 2015 Accepted: September 19, 2015 Published: October 15, 2015 ABSTRACT Objective and Methods: In this phase 1b study, patients with stage 4 or unresectable stage 3 melanoma were treated with escalating doses of lenvatinib (once daily) and temozolomide (TMZ) (days 1–5) in 28-day cycles, to determine the maximum tolerated dose (MTD) of the combination. Dose Level (DL)1: lenvatinib 20 mg, TMZ 100 mg/m 2 ; DL2: lenvatinib 24 mg, TMZ 100 mg/m 2 ; DL3: lenvatinib 24 mg, TMZ 150 mg/m 2 . Adverse events (AEs) were recorded and tumor response assessed per RECIST 1.0. Results: Dose-limiting toxicity occurred in 1 of 32 treated patients (DL1); MTD was not reached. The highest dose administered was lenvatinib 24 mg + TMZ 150 mg/m 2 . Most common treatment-related AEs included fatigue (56.3%), hypertension (53.1%), and proteinuria (46.9%). Overall objective response rate was 18.8% (6 patients), all partial response; (DL1, n = 1; DL3, n = 5). Stable disease (SD) ≥ 16 weeks was observed in 28.1% of patients (DL1 and DL2, n = 1 each; DL3, n = 7); 12.5% of patients had SD ≥ 23 weeks. Single and repeat-dose pharmacokinetics of lenvatinib were comparable across cycles and with concomitant TMZ administration. Conclusion: Lenvatinib 24 mg/day + TMZ 150 mg/m 2 /day (days 1–5) demonstrated modest clinical activity, an acceptable safety profile, and was administered without worsening of either lenvatinib- or TMZ-related toxicities in this patient group.
Source: Oncotarget
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2264854570