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
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract
5368 - Durvalumab and Paclitaxel Combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy
Presenter: Hazem Ghebeh
Session: Poster Display session 3
Resources:
Abstract
1520 - A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
Presenter: Daan Hurkmans
Session: Poster Display session 3
Resources:
Abstract
1603 - Safety and clinical activity of subcutaneously (SC) administered anti-PD-1 antibody PF-06801591 in phase I dose-expansion cohorts of locally advanced or metastatic non-small-cell lung cancer (NSCLC) and urothelial carcinoma (UC)
Presenter: Byoung Cho
Session: Poster Display session 3
Resources:
Abstract
3922 - Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A scale to measure quality of life in cancer patients treated with ICMs
Presenter: Aaron Hansen
Session: Poster Display session 3
Resources:
Abstract
2408 - Immune checkpoint inhibitors (ICIs) as “chemotherapy (Ctx) sensitization” strategy in advanced solid tumors
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 3
Resources:
Abstract
3612 - Validation of progression-free survival (PFS) as surrogate endpoint in randomised trials of immune checkpoint inhibitors in advanced solid cancers
Presenter: Peey Sei Kok
Session: Poster Display session 3
Resources:
Abstract
3827 - Pharmacokinetic (PK) analysis of weight-based and fixed dose cemiplimab in patients (pts) with advanced malignancies
Presenter: Michael Migden
Session: Poster Display session 3
Resources:
Abstract
2120 - A burst of highly differentiated CD4 TL identifies a subset of fast progressors, and correlates with hyperprogressive disease in NSCLC patients treated with ICI
Presenter: Hugo Arasanz
Session: Poster Display session 3
Resources:
Abstract
4254 - Nivolumab treatment in advanced non-small cell lung cancer (aNSCLC): a French nationwide retrospective cohort (UNIVOC Study)
Presenter: Christos Chouaid
Session: Poster Display session 3
Resources:
Abstract