Abstract 4596
Background
Melanoma that metastasizes to the brain has a poor prognosis, and accounts for up to 54% of melanoma deaths. Clinical data show that treatment with BRAF-targeted agents induces responses in RAFV600-mutant MBM. Duration of response in the brain is shorter than that observed with extracranial disease. The BRAF/MEK-targeted combination encorafenib + binimetinib demonstrated favorable efficacy and safety for patients with BRAFV600-mutant melanoma in the COLUMBUS study, but excluded patients with active MBM. The aim of this study is to evaluate encorafenib + binimetinib in a population of patients with BRAFV600-mutated active MBM. A higher dose of combination therapy will be studied versus a standard dose to evaluate whether greater efficacy may be achieved with acceptable safety for patients with BRAFV600 MBM.
Trial design
This multicenter, randomized, open-label phase II study will evaluate two dosing regimens of encorafenib + binimetinib combination in adults with BRAFV600-mutant MBM. Eligible patients will have at least 1 measurable MBM, no prior local MBM therapy, no corticosteroids for MBM, and no prior BRAF or MEK inhibitors in the metastatic setting. One prior line of checkpoint inhibitor or prior adjuvant BRAF or MEK inhibitors is permitted. Patients will be randomized (1:1) to either the standard dose (450 mg orally QD and binimetinib 45 mg orally BID) or high-dose (encorafenib 300 mg BID and binimetinib 45 mg BID) stratified by baseline tumor burden (1 to 2 brain lesions vs. ≥ 3 brain lesions at baseline) and by prior checkpoint inhibitor (yes vs. no). The first 9 evaluable patients in the high-dose arm will constitute the safety lead-in cohort. If the high-dose is not tolerated, subsequent patients will receive standard-dose therapy. Assessments include intracranial response (assessed as per modified RECIST using gadolinium enhanced MRI), extracranial response, global response rate, DCR, DOR, PFS, OS, PK, and safety. The study will enroll approximately 100 patients.
Clinical trial identification
NCT03911869
Editorial acknowledgement
JD Cox and Mayville Medical Communications, with funding from Array Biopharma.
Legal entity responsible for the study
Array BioPharma Inc.
Funding
Array BioPharma Inc.
Disclosure
M.A. Davies: Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Syndax; Non-remunerated activity/ies: Nanostring. J.S. Weber: Advisory / Consultancy, Research grant / Funding (institution): Array BioPharma; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech. K.T. Flaherty: Officer / Board of Directors: Clovis Oncology; Officer / Board of Directors: Strata Oncology; Officer / Board of Directors: Vivid Biosciences; Officer / Board of Directors: Checkmate Pharmaceuticals; Advisory / Consultancy: X4; Advisory / Consultancy: PIC Therapeutics; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Asana; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Fount; Advisory / Consultancy: Aeglea; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Shattuck Labs; Advisory / Consultancy: Tolero; Advisory / Consultancy: Apricity; Advisory / Consultancy: Oncoceutics; Advisory / Consultancy: Fog Pharma; Advisory / Consultancy: Neon; Advisory / Consultancy: Tyardi. G.A. McArthur: Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Pfizer. M.B. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Array BioPharma. A. Golden: Shareholder / Stockholder / Stock options, Full / Part-time employment: Array BioPharma. J.L. Culbertson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Array BioPharma. C.T. Thomas: Shareholder / Stockholder / Stock options, Full / Part-time employment: Array BioPharma. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Array BioPharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): GSK. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncosec; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche.
Resources from the same session
5218 - Elevated driver mutational burden or number of perturbed pathways and poor response to abiraterone or enzalutamide in metastatic castration-resistant prostate cancer
Presenter: Bram De Laere
Session: Poster Display session 3
Resources:
Abstract
2452 - High proportion of multiple KRAS mutations in circulating tumor DNA and tumor tissue of pancreatic ductal adenocarcinoma
Presenter: Min Kyeong Kim
Session: Poster Display session 3
Resources:
Abstract
3328 - Biological difference of tumor mutational burden (TMB) and microsatellite instability (MSI) status in patients (pts) with somatic vs. germline BRCA1/2-mutated advanced gastrointestinal (GI) cancers using cell-free DNA (cfDNA) sequencing analysis in the GOZILA study
Presenter: Yasuyuki Kawamoto
Session: Poster Display session 3
Resources:
Abstract
3022 - Cell-Free DNA to Detect Focal Versus Non-Focal MET Amplification in Metastatic Colorectal Cancer Patients: Combined Analysis from Japan and the United States
Presenter: Mishima Saori
Session: Poster Display session 3
Resources:
Abstract
2833 - Presence of circulating tumor DNA in surgically resected renal cell carcinoma is associated with advanced disease and poor patient prognosis
Presenter: Andres Correa
Session: Poster Display session 3
Resources:
Abstract
1376 - Combined genomic and epigenomic assessment of cell-free circulating tumor DNA (cfDNA) for cancer diagnosis and recurrence-risk assessment in early-stage lung cancer
Presenter: Junghee Lee
Session: Poster Display session 3
Resources:
Abstract
4050 - DEMo: a prospective evaluation of a prognostic clinico-molecular composite score in NSCLC patients treated with immunotherapy.
Presenter: Arsela Prelaj
Session: Poster Display session 3
Resources:
Abstract
4727 - Bespoke circulating tumor DNA (ctDNA) analysis as a predictive biomarker in solid tumor patients (pts) treated with single agent pembrolizumab (P)
Presenter: Cindy Yang
Session: Poster Display session 3
Resources:
Abstract
3662 - Dynamic changes in whole-genome cell-free DNA (cfDNA) to identify disease progression prior to imaging in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3817 - Evaluation of Microsatellite Instability Testing Through cell-free DNA sequencing
Presenter: Shile Zhang
Session: Poster Display session 3
Resources:
Abstract