Data from the pivotal coBRIM Phase III study, presented by Lead Investigator Dr James Larkin 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, 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.

Watch the interview with Dr Larkin for more.

References

1. Larkin J et al. Update of progression-free survival and correlative biomarker analysis from coBRIM: Phase III study of cobimetinib plus vemurafenib in advanced BRAF-mutated melanoma. Abstract presented at ASCO, Chicago, IL, USA, 29 May – 2 June 2015; abstract #9006

2. Pavlick AC et al. Extended follow-up results of phase 1B study (BRIM7) of vemurafenib with cobimetinib in BRAF-mutant melanoma. Abstract presented at ASCO, Chicago, IL, USA, 29 May – 2 June 2015; abstract #9020

3. Algazi AP et al. Treatment of cutaneous melanoma: current approaches and future prospects. Cancer Manag Res. 2010;2:197-211

4. Rigel D. Malignant melanoma: Perspectives on incidence and its effects on awareness, diagnosis, and treatment. CA: A Cancer Journal for Clinicians. 1996:46:195-198

5. McArthur GA et al. Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3 randomised, open-label study. Lancet Oncology. 2014;15:323-32

6. Cancer Research UK. Two young adults diagnosed with skin cancer every day. Available at http://www.cancerresearchuk.org/about-us/cancer-news/press-release/two-young-adults-diagnosed-with-skin-cancer-every-day [Last accessed: May 2015]

7. Mistry M et al. Cancer incidence in the United Kingdom: projections to the year 2030. British Journal of Cancer. 2011;105:1795-1803

8. Larkin J et al. Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma. N Engl J Med. 2014;371(20):1867-76

9. National Institutes of Health. A phase 3 study comparing GDC-0973, a MEK inhibitor, in combination with vemurafenib vs. vemurafenib alone in patients with metastatic melanoma. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01689519  [Last accessed: May 2015]

10. Zelboraf Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/ Last accessed May 2015.

11. Heinzerling L et al. Rare BRAF mutations in melanoma patients: implications for molecular testing in clinical practice. British Journal of Cancer. 2013108,2164–2171

12. Johnston S. XL518, a potent, selective, orally bioavailable MEK1inhibitor, down regulates the Ras/Raf/MEK/ERK pathway in vivo, resulting in tumor growth inhibition and regression in preclinical models. Poster presented at AACR-NCI-EORTC, San Francisco, CA, USA. 22 October 2007; abstract #C209

Source: Roche