2014年7月22日訊 /生物谷BIOON/ --葛蘭素史克（GSK）近日宣布，獨立數據監測委員會（IDMC）已建議III期COMBI-v（MEK116513）提前終止。COMBI-v是一項III期研究，在BRAF V600E或V600K突變陽性不可切除性或轉移性黑色素瘤患者中開展，調查了黑色素瘤藥物Mekinist（trametinib）+Tafinlar（dabrafenib）組合療法相對於vemurafenib的療效。
IDMC的積極建議，是基於COMBI-v的一項既定中期分析的積極數據。該分析數據證明，與vemurafenib相比，Mekinist+Tafinlar組合療法在橫跨既定療效終止邊界均表現出總生存期（OS）利益。進一步的療效和安全性數據分析正在進行中，預計將在未來幾個月內完成。該項研究中，vemurafenib治療組的患者將被允許接受Mekinist+Tafinlar組合療法治療。
關於COMBI-v：
COMBI-v是一項隨機、開放標籤III期研究，在BRAF V600E或V600K突變陽性不可切除性或轉移性皮膚黑色素瘤患者中開展，調查了Mekinist+Tafinlar組合療法相對於vemurafenib的療效。該項研究中所招募的704例患者來自美國、歐洲、加拿大、俄羅斯、烏克蘭、以色列、阿根廷、巴西、韓國、紐西蘭、中國臺灣和澳大利亞等地的研究中心。研究的主要目標是評估總生存期（OS），次要終點包括無進展生存期（PFS）、總緩解率（ORR）及緩解持續時間。
關於Tafinlar和Mekinist：
Tafinlar和Mekinist是GSK研發的2款黑色素瘤新藥，均於2013年5月獲FDA批准。Tafinlar為BRAF抑制劑，作為一種單藥口服膠囊，適用於攜帶BRAF V600E突變的手術不可切除性黑色素瘤或轉移性黑色素瘤成人患者的治療。Mekinist為首個MEK抑制劑，作為一種單藥口服片劑，適用於攜帶BRAF V600E或V600K突變的手術不可切除性黑色素瘤或轉移性黑色素瘤成人患者的治療。
Tafinlar不適用於野生型BRAF黑色素瘤患者的治療。Mekinist不適用於既往接受過BRAF抑制劑療法的患者的治療。
轉移性黑色素瘤中，約有一半攜帶BRAF突變，該異常突變能促使黑色素瘤生長和擴散。Tafinlar和Mekinist分別獲批用於攜帶BRAF V600E突變的患者，該突變約佔轉移性黑色素瘤所有BRAF V600突變的85%。Mekinist同時獲批用於攜帶BRAF V600K突變的患者，該突變約佔轉移性黑色素瘤所有BRAF V600突變的10%。（生物谷Bioon.com）
英文原文：Trametinib (Mekinist™) and dabrafenib (Tafinlar™) combination demonstrated overall survival benefit compared to vemurafenib; phase III BRAF V600-mutant metastatic melanoma study stopped early
GlaxoSmithKline plc (LSE/NYSE: GSK) announced today that the Independent Data Monitoring Committee (IDMC) recommended COMBI-v (MEK116513), a phase III study of its MEK inhibitor, trametinib (Mekinist™), in combination with its BRAF inhibitor, dabrafenib (Tafinlar™), compared to vemurafenib in patients with BRAF V600E or V600K mutation-positive unresectable or metastatic cutaneous melanoma be stopped early. This IDMC recommendation is based on an interim analysis which demonstrated an overall survival benefit for the trametinib and dabrafenib combination compared to vemurafenib that crossed the pre-specified efficacy stopping boundary. The safety profile of the trametinib and dabrafenib arm was consistent with the safety profile of the combination observed to date.
The IDMC recommendation today is based on headline data; further analysis of safety and efficacy data is underway and will be completed in the coming months. Eligible study patients who were randomised to the vemurafenib arm will be allowed to cross over to receive treatment with the trametinib and dabrafenib combination.
Dr. Rafael Amado, Head of Oncology R&D at GSK, said: 「Today’s headline results for the combination of dabrafenib and trametinib add to the body of evidence our phase III program has provided thus far, which we hope will more fully characterise the efficacy and safety profile of this combination for patients with BRAF V600-mutant metastatic melanoma. We will continue to analyse this data versus vemurafenib over the coming months and look forward to sharing these with the scientific community once the analysis is complete.」
About COMBI-v
This phase III, randomised, open-label study compared the combination of dabrafenib and trametinib to vemurafenib in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. COMBI-v enrolled 704 patients from investigative sites in the U.S., Europe, Canada, Russia, Ukraine, Israel, Argentina, Brazil, Korea, New Zealand, Taiwan, and Australia.
The primary objective of the study was to evaluate dabrafenib and trametinib combination therapy vs. vemurafenib with respect to OS. Secondary objectives evaluated and compared dabrafenib and trametinib combination therapy versus vemurafenib with respect to progression-free survival, overall response rate, and duration of response. The safety of dabrafenib and trametinib combination therapy, including incidences of squamous cell carcinoma and other proliferative skin diseases, was also evaluated.
About cutaneous melanoma
Cutaneous melanoma is the most aggressive form of all skin cancers. Worldwide, it is expected that over 132,000 people will be diagnosed with melanoma each year and more than 37,000 people are expected to die of this tumour disease annually. In the U.S. and most countries of the Western World including Australia, the incidence of melanoma continues to rise faster than any other type of cancer in men and the annual increase in the incidence of melanoma in women is second only to lung cancer.
About trametinib (Mekinist™) and dabrafenib (Tafinlar™)
Combination use of trametinib and dabrafenib in patients with unresectable or metastatic melanoma who have BRAF V600E or K mutation is approved only in the U.S. and Australia.
Trametinib was in-licensed by GSK in 2006 from Japan Tobacco Inc. (JTI). GSK holds the worldwide exclusive rights to develop, manufacture, and commercialise trametinib, while JTI retains co-promotion rights in Japan.
Tafinlar and Mekinist are registered trademarks of the GSK group of companies.