On November 23, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from a phase Ib study of the investigational cancer immunotherapy atezolizumab (MPDL3280A), used in combination with the BRAF inhibitor Zelboraf (vemurafenib) for previously untreated BRAFV600 mutation-positive unresectable or metastatic melanoma (Press release, Hoffmann-La Roche , NOV 23, 2015, View Source [SID:1234508314]). Schedule your 30 min Free 1stOncology Demo! Adverse events (AEs) were manageable and generally reversible. The study also showed that the combination resulted in an objective response rate [ORR] of 76% (95% confidence interval [CI:] 50.1%–93.2%) of people (n=17), including three complete responders (CR). The data were presented at the Society of Melanoma Research (SMR) 2015 International Congress.1
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"These early efficacy results encourage us to further evaluate combination strategies of atezolizumab and targeted therapies like Zelboraf in people living with advanced melanoma, a disease which is still associated with a poor prognosis", Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development.
Roche is also investigating a triplet regimen with atezolizumab plus the established targeted therapy combination of Zelboraf and Cotellic (cobimetinib), a selective MEK inhibitor, in a phase Ib study.
About the phase Ib study of atezolizumab in combination with Zelboraf
This phase Ib, open-label study aimed to evaluate the safety and pharmacology of atezolizumab in combination with Zelboraf in patients with previously untreated BRAFV600 mutation-positive metastatic melanoma
17 patients were evaluable for safety and efficacy at the time of this data cut
Patients received atezolizumab combined with Zelboraf concurrently (Cohort 1 [C1], n=3) or after a run-in period with Zelboraf alone of 56 days (Cohort 2 [C2]; n=8) or 28 days (Cohort 3 [C3]; n=6)
Patients were given atezolizumab intravenously every 3 weeks at 20 mg/kg (C1) or 15 mg/kg (or 1,200 mg fixed; C2/C3). Oral Zelboraf was given twice daily at 960 mg during the run-in period and at 720 mg during atezolizumab and Zelboraf combined treatment
PD-L1 expression was centrally assayed using immunohistochemistry (IHC; SP142 assay)
About BRAFV600 mutation-positive metastatic melanoma
Melanoma is less common, but more aggressive and deadlier, than other forms of skin cancer.2,3 A mutation of the BRAF protein occurs in approximately half of melanomas, and a test can be used to determine who can be treated with a BRAF-inhibitor.4 When melanoma is diagnosed early, it is generally a curable disease,5,6 but most people with advanced melanoma have a poor prognosis.3 More than 232,000 people worldwide are currently diagnosed with melanoma each year.7 In recent years, there have been significant advances in treatment for metastatic melanoma, and people with the disease have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years.8
About atezolizumab
Atezolizumab (also known as MPDL3280A) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.
About Zelboraf
Zelboraf was the first approved treatment for patients with unresectable or metastatic melanoma with BRAFV600 mutation as detected by a validated test, such as Roche’s cobas 4800 BRAF Mutation Test. Zelboraf is not indicated for use in patients with wild-type BRAF melanoma.
About Cotellic plus Zelboraf
Cotellic and Zelboraf are used in combination to treat unresectable or metastatic melanoma with BRAFV600 mutation. Found in approximately half of melanomas, mutated BRAF causes abnormal signalling inside certain cancer cells leading to tumour growth. Zelboraf binds to mutant BRAF, to interrupt abnormal signalling that can cause tumours to grow.9,10 Cotellic is designed to inhibit some forms of MEK. Both BRAF and MEK are proteins in a cell signalling pathway that help control cell growth and survival. When used in combination, Cotellic and Zelboraf are thought to reduce cancer cell growth longer than Zelboraf alone. A patient’s healthcare provider will perform a test to make sure Cotellic and Zelboraf are right for the patient. It is not known if Cotellic and Zelboraf are safe and effective in children under 18 years of age.
Cotellic was approved in Switzerland in August 2015 and in the US in November 2015. In September, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA) issued a positive opinion for Roche’s marketing authorisation application for Cotellic in the European Union. A decision from the European Commission is expected before the end of 2015.