Swiss drug maker Roche has reported positive data from the coBRIM Phase III trial of the combination of cobimetinib and Zelboraf (vemurafenib) to treat patients with BRAF V600 mutation-positive advanced melanoma.
The international, randomised, double-blind, placebo-controlled trial evaluated the safety and efficacy of 60mg once daily of cobimetinib in combination with 960mg twice daily of Zelboraf, compared to 960mg twice daily of Zelboraf alone.
Results showed that people with previously untreated BRAF V600 mutation-positive, advanced melanoma who received the combination therapy lived significantly longer without their disease worsening or death (progression-free survival; PFS) compared to Zelboraf alone.
During the trial, around 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma and previously untreated for advanced disease, were given Zelboraf every day on a 28-day cycle plus either cobimetinib or placebo on days one to 21.
The combined therapy reduced the risk of disease worsening or death by half, with a median PFS of 9.9 months for cobimetinib plus Zelboraf compared to 6.2 months with Zelboraf alone.
Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent, while the investigator-evaluated PFS was the primary endpoint.
Apart from PFS by independent review committee (IRC), objective response rate (ORR) and overall survival (OS), secondary endpoints included duration of response and other safety, pharmacokinetic and quality of life measures.
Roche chief medical officer and head of Global Product Development Dr Sandra Horning said: "We combined cobimetinib and Zelboraf in this study to better inhibit a major cancer growth pathway and hopefully improve clinical outcomes.
"The coBRIM results are exciting because they support the potential of the combination as a new treatment option for people with BRAF mutation-positive advanced melanoma."
Most common adverse events observed in the combination arm included diarrhoea, nausea, rash, photosensitivity, and lab abnormalities.
The company has also submitted an EU marketing authorisation application for the combination drug to treat BRAF V600 mutation-positive advanced melanoma.
Data from the coBRIM study was submitted to the European Medicines Agency and the company intends to submit a new drug application (NDA) to the US Food and Drug Administration later this year.
Image: Melanoma in skin biopsy with H&E stain -- this case may represent superficial spreading melanoma. Photo: courtesy of KGH