On November 7, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from two early cancer immunotherapy studies at the International Congress of the Society for Melanoma Research (SMR) (Press release, Hoffmann-La Roche, NOV 7, 2016, View Source [SID1234516330]). These early studies of clinical efficacy and safety for combinations including TECENTRIQ (atezolizumab), Cotellic (cobimetinib) and ZelborafTM (vemurafenib), are advancing the development of new treatment approaches while broadening the understanding of melanoma. In addition, three-year data from the phase III coBRIM study were presented, confirming the long-term overall survival benefit of Cotellic plus Zelboraf in BRAFV600 mutation positive advanced or metastatic melanoma.

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Safety and efficacy results from 30 patients in a phase Ib study of the combination of TECENTRIQ, an anti-PD-L1 monoclonal antibody, with Cotellic, a MEK inhibitor, plus Zelboraf, a BRAF inhibitor, in previously untreated patients with BRAFV600 mutation-positive metastatic melanoma, were presented. Median safety follow-up was 3.9 months (range 0.7-16.8). Grade 3-4 adverse events (AEs) were seen in 40 percent of patients treated with the triple combination; all resolved after appropriate interventions. No unexpected AEs, Grade 5 AEs or TECENTRIQ-related serious AEs occurred. Out of 29 evaluable patients for efficacy, responses were seen in 24 patients (83 percent) with 3 complete responses and 21 partial responses; the majority of patients continued to respond at the time of data cut-off (median follow up of 5.6 months).

Results were also presented from a phase Ib study of TECENTRIQ with Cotellic, including efficacy and safety data for 22 patients with metastatic melanoma (2 ocular, 20 non-ocular with 10 each BRAF-mutant and wild-type). Patients had received a median of 1 prior therapy for melanoma (range 0-8), but had not received prior anti-PD-1/PD-L1 therapy. Median safety follow-up was 14.0 months (range 2.4-20.2 months). Grade 3-4 AEs occurred in 59 percent of patients, no treatment-related Grade 5 AEs were reported; all AEs were manageable. Among the 20 patients with non-ocular metastatic melanoma the objective response rate (ORR) was 45 percent (50 percent in BRAF wild-type and 40 percent in BRAF-mutant patients). The median progression-free survival (PFS) was 12 months in the non-ocular melanoma patients (15.7 months in BRAF wild-type and 11.9 months in BRAF-mutant patients).

"We are encouraged by these early results which demonstrate a high proportion of people responded to these investigational combination therapies," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The results suggest that the combination of TECENTRIQ with our BRAF and MEK targeted agents may extend the established benefits of the approved monotherapy and combination approaches of these medicines."
Based on the promising results of these Phase Ib studies, Roche plans to initiate two Phase III studies of these investigational combinations for patients with metastatic melanoma. These pivotal trials will study TECENTRIQ with Cotellic plus Zelboraf in treatment-naïve, BRAF-mutant metastatic melanoma and TECENTRIQ with Cotellic in treatment-naïve, BRAF wild-type metastatic melanoma.

Additionally, updated OS data from the phase III coBRIM study of Cotellic plus Zelboraf have demonstrated the continuing benefit across all patient subgroups of the combination therapy vs Zelboraf alone, in patients with BRAFV600-mutation positive unresectable locally advanced metastatic melanoma. The percentage of patients alive at three years was 37.4 percent for people treated with Cotellic plus Zelboraf vs 31.1 percent for patients treated with placebo plus Zelboraf. Median OS was 22.5 months for Cotellic plus Zelboraf vs 17.4 months for Zelboraf alone.
Follow Roche on Twitter via @Roche and keep up to date with SMR 2016 congress news and updates by using the hashtag #SMR16.

About Cotellic and Zelboraf in combination
Zelboraf was the first approved treatment for patients with unresectable or metastatic melanoma with BRAF V600 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. Cotellic (cobimetinib) is designed to selectively block the activity of MEK, one of a series of proteins inside cells that make up the MAPK signaling pathway that helps regulate cell division and survival. In the majority of patients, resistance to BRAF-inhibitor monotherapy will eventually occur through re-activation of the MAPK pathway via MEK. Cotellic was developed to overcome resistance to BRAF-inhibition and prevent re-activation of the pathway. Cotellic binds to MEK, while Zelboraf binds to mutant BRAF, to interrupt abnormal signalling that can cause tumours to grow.
Cotellic is also being investigated in combination with several investigational medicines, including immunotherapy, in several tumour types such as non-small cell lung cancer and colorectal cancer. Cotellic was discovered by Exelixis Inc. and is being developed by Roche in collaboration with Exelixis.

About melanoma
Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. A V600 mutation of the BRAF protein occurs in approximately half of melanomas, and should therefore be tested to identify the best treatment option. When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. More than 232,000 people worldwide are currently diagnosed with melanoma each year. 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.