Cotellic is indicated for use in combination with vemurafenib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

...Other regimens (for patients with BRAF V600-activating mutation) with the following agents - Dabrafenib/trametinib...vemurafenib/cobimetinib...Encorafenib/Binimetinib...

Median OS was 22.5 months (95% CI, 20.3-28.8) with cobimetinib plus vemurafenib and 17.4 months (95% CI, 15.0-19.8) with placebo plus vemurafenib; 5-year OS rates were 31% and 26%, respectively. Median PFS was 12.6 months (95% CI, 9.5-14.8) with cobimetinib plus vemurafenib and 7.2 months (95% CI, 5.6-7.5) with placebo plus vemurafenib; 5-year PFS rates were 14% and 10%, respectively. OS and PFS were longest in patients with normal baseline lactate dehydrogenase levels and low tumor burden, and in those achieving complete response. Extended follow-up of coBRIM confirms the long-term clinical benefit and safety profile of cobimetinib plus vemurafenib compared with vemurafenib monotherapy in patients with BRAF V600 mutation-positive advanced melanoma.

In this double-blind, randomised, placebo controlled, multicentre study, adult patients (aged ≥18 years) with histologically confirmed BRAF V600 mutation-positive unresectable stage IIIC or stage IV melanoma were randomly assigned (1:1) using an interactive response system to receive cobimetinib (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle) or placebo, in combination with oral vemurafenib (960 mg twice daily)....495 eligible adult patients were enrolled and randomly assigned to the cobimetinib plus vemurafenib group (n=247) or placebo plus vemurafenib group (n=248)….At a median follow-up of 14·2 months (IQR 8·5–17·3), the updated investigator-assessed median progression-free survival was 12·3 months (95% CI 9·5 13·4) for cobimetinib and vemurafenib versus 7·2 months (5·6–7·5) for placebo and vemurafenib (HR 0·58 [95% CI 0·46–0·72], p<0·0001).

...- Histologically confirmed metastatic melanoma (stage IV, per AJCC staging), carrying BRAF V600-mutation...

...Untreated and pretreated (no more than 1 treatment) patients with metastatic melanoma at stage unreseactable IIIb-IV, histologically confirmed, that show V600 type BRAF mutations....

...- Documentation of BRAF V600 test result mutation-positive status on melanoma tumor tissue using a validated tissue test...

...Any patient with metastatic melanoma (any site) whose tumor is V600EBRAF positive, regardless of prior treatment....

...- Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600-mutation...

...Documented BRAFV600 mutation determined in a hospital center specializing in the molecular genetics of cancer that is certified by the French national cancer institute (INCa)....

...- Diagnosis of BRAFV600 mutated Stage IV or unresectable Stage III melanoma...

...- Melanoma must be documented to contain a BRAFV600 mutation by a FDA approved assay...

...- Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory...

...Confirmed diagnosis of a malignancy harbouring any actionable BRAF V600 mutation using an analytically validated sequencing technique (result does...

...3) Adjuvant treatment is allowed, except for anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 agents4) Patients must be naïve to treatment for locally advanced unresectable or metastatic with BRAF/MEK inhibitors5) Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue BRAF V600 mutation test6) At least one measurable lesion according to disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria7) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0- 28) Male or female patient aged = 18 years9) Able to participate and willing to give written informed consent prior to performance of any study-related procedures and to comply with the study protocol10) Life expectancy = 12 weeks 1) Pazienti con melanoma metastatico di stadio IIIc o IV non resecabile confermato istologicamente secondo la definizione dell'American Joint Committee on Cancer 7ma edizione. ...

...BRAF V600 mutation positive....

...- Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test...

...Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue....

...Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue BRAF V600 mutation test; 6....

Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B….The aim of the present study was, therefore, to collect real-world data on effectiveness of cobimetinib/vemurafenib with a special focus on OS, safety and utilization of the combination therapy in two separate cohorts: patients with unresectable or metastatic BRAF V600 mutated mM without cerebral metastases and patients with metastatic BRAF V600 mutated mM with cerebral metastases.

This was a single arm, prospective, multi centre phase II study in patients with histologically confirmed, BRAF V600 mutated Stage IIIB and IIIC melanoma (AJCC 7th Edition) with palpable nodal disease. Patients received vemurafenib 960mg PO BID and cobimetinib 60mg PO OD for 4 months prior to resection followed by 8 months of adjuvant therapy post-surgery....At 60 months, LRFS was 89.5% (76.7-100%), DMFS was 75.0% (59.5-94.5%), DFS was 85.7% (72.0-100%), and OS was 63.9% (95% CI 43.5-93.8). Among total 20 evaluable patients, 17 patients had CR/PR and 3 had PD/SD as best response.

This was a single arm, prospective, multi centre phase II study in patients with confirmed BRAF V600 mutated Stage IIIB and IIIC melanoma…Neoadjuvant vemurafenib and cobimetinib led to all patients being resectable with a high response rate, pathologic response rate and low local recurrence rate in melanoma patients with palpable lymph nodes.

Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a BRAF V600 mutation who initiated a combination therapy with vemurafenib/cobimetinib... During the combination therapy, 12 patients (29.3%) had a CR, 19 a PR (46.3%), 5 showed SD (12.2%), and 5 had PD....The combination treatment with vemurafenib/cobimetinib results in an important impact on long-term survival, leading to a steady CR in one-third of the patients.

Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a BRAF V600 mutation who initiated a combination therapy with vemurafenib/cobimetinib...During the combination therapy, 12 patients (29.3%) had a CR, 19 a PR (46.3%), 5 showed SD (12.2%), and 5 had PD. A total of 12 patients (29.3%) were considered as achieving a durable response and 29 (70.7%) as a non-durable one.

Participants were patients with advanced melanoma harboring a BRAF V600 mutation, who received Cobimetinib + Vemurafenib as first line, and who started treatment at least 12 months before inclusion....CR was the best response achieved by 29.3% of patients, 46.3% achieved PR and 12.2% SD (stable disease). Mean of time to response was 6.9 months for CR patient, and 3.3 and 2.2 months for PR and SD patients respectively. Mean of duration of response was 9.4 months for CR patients, and 10.1 and 9.5 months for PR and SD patients respectively....Vemurafenib and Cobimetinib have an important impact in long term survival, leading to a steady complete response in one third of the patients.

...a phase 1b study in patients with advanced BRAF(V600)-mutated melanoma...patients received vemurafenib 720 mg or 960 mg twice a day continuously and cobimetinib 60 mg, 80 mg, or 100 mg once a day for either 14 days on and 14 days off (14/14), 21 days on and 7 days off (21/7), or continuously (28/0)....Confirmed objective responses were recorded in ten (15%) of 66 patients who had recently progressed on vemurafenib, with a median progression-free survival of 2·8 months (95% CI 2·6-3·4). Confirmed objective responses were noted in 55 (87%) of 63 patients who had never received a BRAF inhibitor, including six (10%) who had a complete response; median progression free survival was 13·7 months (95% CI 10·1 17·5)....The combination has promising antitumour activity and further clinical development is warranted in patients with advanced BRAF(V600)-mutated melanoma...