414TiP - An open-label phase 2a study of combination dabrafenib (D) and trametinib (T) in Asian patients (pts) with advanced BRAF V600–mutant acral lentigin...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anticancer agents
Biomarkers
Skin Cancers
Presenter Jun Guo
Citation Annals of Oncology (2016) 27 (suppl_9): ix126-ix129. 10.1093/annonc/mdw589
Authors J. Guo1, W. Chang2, A. Dechaphunkul3, Y. Fan4, T.M. Kim5, C. Lin6, J. Maneechavakajorn7, S.J. Shin8, X. Song9, S. Cheng10, S. Thongprasert11, C.S. Wong12, D. Wu13, X. Zhang14, S. Bettinger15, P. Zhang16, B. Mookerjee16
  • 1Urology And Melanoma, Beijing Cancer Hospital, 100142 - Beijing/CN
  • 2Linkou Branch, Chang Gung Medical Foundation, 333 - Taoyuan/TW
  • 3Oncology Unit, Prince of Songkla University, 90110 - Hat Yai/TH
  • 4Oncology, Zhejiang Cancer Hospital, 310022 - Hangzhou/CN
  • 5Oncology, Seoul National University Hospital, 03080 - Seoul/KR
  • 6Oncology, National Taiwan University Hospital, 10002 - Taipei/TW
  • 7Oncology, Rajavithi Hospital, 10400 - Bangkok/TH
  • 8Oncology, Yonsei University Severance Hospital, 03722 - Seoul/KR
  • 9Oncology, Yunnan Cancer Hospital, 650100 - Kunming/CN
  • 10Oncology, Kaohsiung Medical University Hospital, 807 - Kaohsiung/TW
  • 11Oncology, Wattanosoth Hospital, 50300 - Chiang Mai/TH
  • 12Oncology, Tuen Mun Hospital, 999077 - Tuen Mun/HK
  • 13Oncology, The 1st Affiliated Hospital of Jilin, 130021 - Changchun/CN
  • 14Oncology, Sun Yat-Sen University Cancer Center, 510095 - Guangzhou/CN
  • 15Oncology, Novartis Pharma AG, CH-4002 - Basel/CH
  • 16Oncology, Novartis Pharmaceuticals Corporation, 07936 - East Hanover/US

Abstract

Background

ALM, 1 of 4 major histological subtypes of CM, occurs most frequently in individuals with darker skin with CM (40%-50%), including in Asian populations. Randomized phase 2 (BRF113220) and phase 3 (COMBI-d, COMBI-v) studies demonstrating clinical benefit of D+T over BRAF inhibitor monotherapy in pts with BRAF V600–mutant unresectable or metastatic CM led to the approval of the combination in the United States, Australia, Canada, and Europe; however, these studies were conducted primarily in Caucasian populations. Thus, data for D+T in non-Caucasian populations and in pts with ALM are limited. As efficacy and safety of D+T still needs to be evaluated in Asian pts with melanoma, an urgent unmet medical need remains in countries where this combination is not yet approved.

Trial design

Here, an ongoing single-arm, open-label, multicenter phase 2a study evaluating D+T in Asian pts with histologically confirmed stage IIIC (unresectable) or stage IV BRAF V600–mutant ALM or CM (NCT02083354) is described. Prior systemic anticancer treatment in the adjuvant or metastatic setting is permitted; however, pts with previous exposure to BRAF or MEK inhibitors are ineligible. Enrolled pts are orally administered D 150 mg twice daily and T 2 mg once daily until disease progression, death, unacceptable toxicity, withdrawal of consent, or study completion. The primary endpoint of this study is overall response rate per RECIST v1.1. Secondary endpoints include progression-free survival, duration of response, overall survival, pharmacokinetics, pharmacodynamics, and safety. This ongoing trial will be conducted at 14 centers in the following cities: Beijing, Changchun, Guangzhou, Hangzhou, Kunming (mainland China); Hong Kong; Kaohsiung, Taipei, Taoyuan (Taiwan); Seoul (Korea); Bangkok, Hat Yai (Thailand).

Clinical trial indentification

NCT02083354 (first received February 13, 2014).

Legal entity responsible for the study

Novartis Pharmaceuticals

Funding

Novartis Pharmaceuticals

Disclosure

J. Guo: Declares consultancy with MSD, Novartis, Pfizer, Bayer and Bristol-Myers Squibb. S. Bettinger: Disclose employment at Novartis Pharma AG. P. Zhang: Disclose employment at Novartis. B. Mookerjee: Disclose employment, stocks and long-term investment at Novartis; equity ownership of Novartis, GSK, Incite, Astra Zeneca. All other authors have declared no conflicts of interest.