Brain Metastases (BM) occur in 10 to 20% of patients (pts) at initial diagnosis of metastatic melanoma (MM) and develop in up to 73% of pts with MM.
BRAFV600 mutations are found in around 50% of cutaneous melanomas. Vemurafenib, a BRAF inhibitor, is a standard 1st-line treatment of BRAFV600 MM in Europe, and recent data suggest a benefit for patients with BM.
Resistance to a monotherapy with a BRAF inhibitor is frequent. Results of a phase III trial comparing vemurafenib + cobimetinib (MEK inhibitor) to vemurafenib in pts with BRAF mutated MM showed improved PFS and OS. Patients with symptomatic BM were excluded from this study.
The objective of CONVERCE, a phase II interventional study, is to determine whether the combination of vemurafenib + cobimetinib is effective in the treatment of BRAFV600 mutated melanoma with BM.
Pts with histologically confirmed metastatic cutaneous melanoma, mucosal melanoma, or melanoma of unknown primary origin, and BM for which surgical resection is not a reasonable option, will be enrolled into 3 cohorts (n = 137): neurologically asymptomatic pts with previously locally untreated (Cohort A) or treated (Cohort B) BM, and neurologically symptomatic patients with previously locally treated or not BM (Cohort C). Pts will be treated with vemurafenib 960 mg PO, twice daily from D1 to D28, continuously, and cobimetinib 60 mg PO, once daily, from D1 to D21 (1 cycle = 28 days) until progression (intracranial or extracranial), unacceptable toxicity, withdrawal of consent, death or decision of the investigator. The primary endpoint is the complete or partial intracranial response rate in cohort A based on the evaluation of patient's best tumor response assessed by the centralized review committee according to modified RECIST 1.1 criteria). Secondary endpoints include objective intracranial response rates in cohorts B and C; intracranial duration of response, progression-free survival, overall response rate and overall survival in all cohorts; safety; pharmacokinetic study including cerebrospinal fluid, kinetic study of BRAF mutation rate in circulating tumor DNA; pharmacogenetics study. Preliminary results are expected in 2018.
Clinical trial identification
ClinicalTrials.gov Identifier: NCT02537600
Legal entity responsible for the study
T. Lesimple: Roche, BMS, Novartis, MSD. A. Mahmoudi: Roche. C. Lebbe: Roche, BMS, Novartis, MSD, Amgen. All other authors have declared no conflicts of interest.