Oral cancer therapy combination prevents progression of advanced melanoma for over a year

Cobimetinib and Zelboraf®* (vemurafenib) target MEK and BRAF cell signals respectively to prevent disease progression in most aggressive form of skin cancer

Data from the pivotal coBRIM Phase III study, presented by Lead Investigator Dr James Larkin today at the American Society of Clinical Oncology (ASCO) annual meeting, demonstrate that Roche's investigational MEK inhibitor cobimetinib, used in combination with BRAF inhibitor vemurafenib, typically offers people with previously untreated advanced metastatic melanoma (BRAFV600 mutation-positive unresectable or metastatic) one full year (median 12.3 months) without their disease worsening.¹ These results show that experimental combination treatment with the oral, targeted therapies can halt disease progression longer than the current standard treatment with a BRAF inhibitor alone.

Dr James Larkin, Consultant Medical Oncologist at The Royal Marsden and Lead Investigator of the coBRIM study said "The results of the coBRIM study reinforce that our continued attention and focus on this disease is providing the clinical advances we need to improve the quality of life and survival for people with melanoma across the UK. Targeting two parts of this cellular pathway, by adding cobimetinib in combination with vemurafenib, sees patients live on average for over a year without their disease progressing - an important advance in melanoma, a significantly life-limiting cancer."

The updated results from coBRIM also demonstrated higher response rates with cobimetinib and vemurafenib compared to vemurafenib alone, a current treatment option for patients with BRAF mutated melanoma. The objective response rate (ORR) with the combination was 70 per cent (16 per cent complete response [CR], 54 per cent partial response [PR]) compared to 50 per cent (11 per cent CR, 40 per cent PR) in the vemurafenib arm (p<0.0001).¹ Importantly, complete response in some patients was not achieved until after more than one year of combination treatment. The safety profile of cobimetinib and vemurafenib was consistent with safety data previously reported. The most common adverse events in the combination arm were diarrhoea, rash, nausea, fever, sun sensitivity, liver laboratory abnormalities, elevated creatine phosphokinase (CPK, an enzyme released by muscles) and vomiting. Overall survival (OS) figures for the coBRIM study will be available later this year.

Another study presented today, follow-up data from the Phase Ib BRIM7 study, showed cobimetinib plus vemurafenib helped people who had not been previously treated with a BRAF inhibitor live a median of more than two years (28.5 months). In addition, extended follow-up showed 61 per cent of patients who had not been previously treated with a BRAF inhibitor were alive after two years.² The safety profile was consistent with the previous analyses. The incidence of serous retinopathy, cardiomyopathy and skin squamous carcinoma were similar to those previously reported.

The European Medicines Agency is expected to make a decision on Roche's marketing authorisation application for cobimetinib in combination with vemurafenib, for BRAFV600 mutation-positive unresectable or metastatic melanoma, before the end of 2015. A new drug application for cobimetinib was granted priority review by the US Food and Drug Administration and a decision is expected in August 2015.

A copy of the Summary of Product Characteristics for vemurafenib is available at http://www.medicines.org.uk/emc/medicine/26056

About metastatic melanoma

Metastatic (or advanced) melanoma is the deadliest and most aggressive form of skin cancer.³ Melanoma is often underestimated and under-recognised.⁴ Until recently, a person with metastatic melanoma has had a short life expectancy, in most cases less than a year.⁵ Many patients are young and in the prime of their lives,⁶ so the disease has a devastating effect on both them and their families. It is estimated that overall cases of melanoma will rise by 52% from 2007 to 2030 - the biggest projected increase of any cancer.⁷

About the CoBRIM study

CoBRIM is an international randomised, double-blind, placebo-controlled Phase III study evaluating the safety and efficacy of cobimetinib in combination with vemurafenib, compared to vemurafenib alone, in 495 patients with BRAFV600 mutation-positive unresectable locally advanced or metastatic melanoma, previously untreated for advanced disease, including patients from 11 UK trial centres.^{8, 9} The primary endpoint for coBRIM is progression free survival. Secondary endpoints are overall survival, objective response rate, duration of response and other safety, pharmacokinetic and quality of life measures.^{8, 9}

About vemurafenib

Vemurafenib is the first personalised treatment to extend the lives of patients with BRAFV600 mutation-positive unresectable or metastatic melanoma for more than one year and the first new treatment in the first-line setting for 30 years.^{5, 10} Vemurafenib is indicated in monotherapy for the treatment of adult patients with BRAFV600 mutation-positive unresectable or metastatic melanoma and is a four-pill regimen taken twice a day that potentially reduces tumour size by blocking the signalling of the abnormal BRAF protein.¹⁰ Mutation of the BRAF gene is present in approximately 40% of all patients with melanoma.¹¹

About cobimetinib

Cobimetinib (GDC-0973) is a novel and selective MEK inhibitor, which in combination with other medicines, may enhance anti-tumour activity and inhibit mechanisms of resistance.¹² In the majority of patients, resistance to BRAF inhibitors will occur through re-activation of the MAPK pathway. Dual inhibition of this pathway with vemurafenib and cobimetinib may delay the onset of resistance and improve patient outcomes.¹²

Adverse event reporting

* This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Roche is committed to the safety of its medicines. As such Roche encourages adverse events to be reported and hence the inclusion of this explanatory information.

Adverse events should be reported. Reporting forms and information can be found at http://www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Roche Products Ltd. Please contact Roche Drug Safety Centre by emailing welwyn.uk_dsc@roche.com or calling 01707 367554.