GSK黑色素瘤组合疗法首个III期研究达主要终点

关键词:葛兰素史克,黑色素瘤,BRAF突变,Tafinlar,Mekinist

2014年1月25日讯 /生物谷BIOON/ --葛兰素史克(GSK)1月24日公布了有关黑色素瘤新药Tafinlar(dabrafenib)+Mekinist(trametinib)组合疗法III期项目首个研究COMBI-d的积极数据。该项研究在BRAF V600E或V600K突变阳性不可切除性或转移性黑色素瘤患者中开展,将Tafinlar+Mekinist组合疗法与Tafinlar单药疗法进行了对比,该项研究达到了疾病无进展生存期(PFS)的主要终点(p<0.05)。此前,Tafinlar+Mekinist组合疗法已获得了FDA的加速批准(accelerated approval)。

该项研究中,组合疗法治疗组PFS、缓解率、中期总生存率数据与I/II期研究中一致,Tafinlar单药治疗组PFS数据比以往Tafinlar单药研究中的PFS数据要大,导致该项研究中PFS组间差异比I/II期研究中的数据更温和。Tafinlar+Mekinist联合治疗组中,最常见的不良反应为发热、乏力、恶心、头痛、寒战、腹泻、关节痛、皮疹、高血压、呕吐。该项研究的完整数据,将提交至即将到来的科学会议

Tafinlar+Mekinist组合疗法用于BRAF V600E/K转移性黑色素瘤的III期项目,包括2个III期研究:COMBI-d(又称MEK115306)和COMBI-v(又称MEK116513):

COMBI-d研究是一项III期、随机、双盲研究,在不可切除性(IIIC阶段)或转移性(IV阶段)BRAF V600E/K突变阳性皮肤黑色素瘤患者中开展,将Tafinlar+Mekinist组合疗法与Tafinlar+安慰剂疗法进行了对比。该项研究的主要终点是疾病无进展生存期(PFS),该项研究同时将随访患者,并计算总生存期。

COMBI-v研究是一项III期、随机、开放标签研究,在不可切除性(IIIC阶段)或转移性(IV阶段)BRAF V600E/K突变阳性皮肤黑色素瘤患者中开展,将Tafinlar+Mekinist组合疗法与BRAF抑制剂vemurafenib进行了对比,主要终点为总生存期,该项研究预计将于2014年获得结果。

目前,Tafinlar+Mekinist组合疗法已获FDA批准用于BRAF V600E/K突变阳性转移性黑色素瘤的治疗。(生物谷Bioon.com)

英文原文:GSK announces headline results for Phase III study of the combination of Tafinlar® (dabrafenib) and Mekinist® (trametinib) in metastatic melanoma

Issued: Friday 24 January 2014, London UK – LSE Announcement

GlaxoSmithKline plc [LSE/NYSE: GSK] today announced that a Phase III study of the combination of Tafinlar® (dabrafenib) and Mekinist® (trametinib), compared to single agent therapy with Tafinlar in patients with BRAF V600 E or K mutation positive unresectable or metastatic melanoma, met its primary endpoint of Progression Free Survival (PFS) (p<0.05).This follows the recent accelerated approval of the combined therapy in the USA.

PFS, response rate and interim overall survival results for the combination arm were consistent with those seen in the Phase I/II study. In this Phase III study, PFS observed among patients in the single agent dabrafenib arm was greater than that seen in previous single agent dabrafenib studies, leading to a more modest difference in PFS between treatment arms than was observed in the Phase I/II study. In the combination arm, the most commonly reported (>20%) adverse events were pyrexia, fatigue, nausea, headache, chills, diarrhoea, arthralgia, rash, hypertension, and vomiting. Full study results will be presented at an upcoming scientific meeting.

“We are pleased to report that the first of our phase III studies investigating the combination of Tafinlar and Mekinist met its primary endpoint. These results, along with data we expect to receive later in the year from our Phase III study comparing the combination to vemurafenib, will increase the body of evidence on the safety and efficacy of this combination in appropriate patients with melanoma,” said Dr Rafael Amado, Senior Vice President Oncology R&D, GSK.

The Phase III programme for dabrafenib and trametinib in BRAF V600E/K metastatic melanoma comprises two studies: COMBI-d (also known as MEK MEK115306) and COMBI-v (also known as MEK116513).

·         Today’s results are from COMBI-d (NCT01584648) a Phase III, randomised, double-blinded study comparing the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to dabrafenib and placebo as first-line therapy in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma.  The primary endpoint of the study is progression-free survival and patients will be followed for overall survival.  The study randomised 423 patients from investigative sites in Australia, Europe, North and South America.

·         COMBI-v (NCT01597908) is a Phase III, randomised, open-label study comparing the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to the BRAF inhibitor vemurafenib in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma.  The primary endpoint of the study is overall survival and results are anticipated in 2014.

Combination use of Tafinlar and Mekinist in patients with BRAF V600E or K metastatic melanoma is approved for use only in the US and is not approved anywhere else in the world.

(责任编辑:lishuheng)

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