Abstract 5479
Background
Over 60% of patients (pts) with stage IV melanoma may develop brain metastases, resulting in a significantly increased morbidity and poor overall prognosis. Clinical data for melanoma brain metastases (MBM) treatments are limited, as controlled studies often exclude pts with untreated brain metastases.
Methods
We conducted a multicenter, retrospective case series investigation with consecutive pts with BRAF-mutant MBM who were treated with BRAF inhibitor encorafenib plus MEK inhibitor binimetinib to evaluate the antitumor response with this combination. Assessments included intracranial, extracranial & global objective response rates (ORRs; percentage of complete [CR] + partial [PR] responses) evaluated by modified RECIST version 1.1; clinical benefit rate (CBR; percentage of CR + PR + stable disease [SD] as best response); time to response, duration of response, and safety.
Results
A total of 17 pts with stage IV BRAF-mutant MBM who received encorafenib plus binimetinib in centers in the United States were included. Pts had received a median of 2 prior lines of treatment over a median of 520 days since their melanoma diagnosis (median of 55 days since diagnosis of MBM). Of the patients included, 82% had prior treatment with BRAF/MEK inhibitors. The intracranial ORR was 35% (with 3 CRs and 3 PRs) and CBR was 76%, with a median duration of response of 17 weeks. Eight pts with either stable disease or a response were still ongoing treatment at the time of this analysis. Among the 14 MBM pts with prior BRAF/MEK inhibitor treatment, the intracranial ORR was 21% and CBR was 71%. Similar outcomes were observed for extracranial and global responses. The safety profile for encorafenib plus binimetinib was similar to that observed in pts with melanoma without brain metastases.
Conclusions
Combination therapy with encorafenib plus binimetinib elicited intracranial activity in pts with BRAF-mutant MBM, including in pts previously treated with BRAF/MEK inhibitors. Further prospective studies are warranted. *K. Holbrook and J. Lutzky are co-first authors.
Clinical trial identification
Editorial acknowledgement
Editorial assistance was provided by JD Cox and Mayville Medical Communications, with funding from Array Biopharma.
Legal entity responsible for the study
Array BioPharma Inc.
Funding
Array BioPharma.
Disclosure
J. Lutzky: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma; Advisory / Consultancy, Speaker Bureau / Expert testimony: Regeneron; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Bristol-Myers Squibb. A. Amin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Regeneron. J.M. Davis: Speaker Bureau / Expert testimony: Exelixis Inc; Advisory / Consultancy: Array BioPharma. 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. A. Diab: Advisory / Consultancy: Array BioPharma. I.C. Glitza: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma. R.N. Amaria: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Iovance. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy, DSMB: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution), DSMB: Reata. 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. All other authors have declared no conflicts of interest.
Resources from the same session
4634 - Comparative molecular analyses between microsatellite stable BRAFV600E mutant colorectal cancers and BRAFV600E mutant melanomas.
Presenter: Mohamed Salem
Session: Poster Display session 3
Resources:
Abstract
3264 - A novel preclinical model of RAF-independent MEK1 mutant tumors and its treatment with novel ATP competitive MEK inhibitor
Presenter: Luca Hegedus
Session: Poster Display session 3
Resources:
Abstract
4918 - HER2 inhibition in Aggressive Squamous Cell Carcinomas driven by a common MET Sema Domain Polymorphism
Presenter: Nur Afiqah Mohamed Salleh
Session: Poster Display session 3
Resources:
Abstract
2426 - ADAM9 as a target for lung cancer treatment
Presenter: Yuh-pyng Sher
Session: Poster Display session 3
Resources:
Abstract
5537 - Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer
Presenter: Marta Perez Hernandez
Session: Poster Display session 3
Resources:
Abstract
1597 - Discovery of Clinical Candidate DBPR112, a Furanopyrimidine-based Epidermal Growth Factor Receptor Inhibitor for the Treatment of Non-Small Cell Lung Cancer
Presenter: Hsing-pang Hsieh
Session: Poster Display session 3
Resources:
Abstract
3543 - Molecular characteristics in lung squamous cell carcinomas dependent on TP53 status – putative targets
Presenter: Vilde Haakensen
Session: Poster Display session 3
Resources:
Abstract
4111 - Comparison of molecular profiles between primary tumour and matched metastasis in non-small cell lung cancer
Presenter: Asuka Kawachi
Session: Poster Display session 3
Resources:
Abstract
4559 - Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in Patients with RET-altered Non-Small Cell Lung Cancer (NSCLC) and Thyroid Cancer
Presenter: Giuseppe Curigliano
Session: Poster Display session 3
Resources:
Abstract
2501 - Triple MET/SRC/PIM inhibition in MET addicted tumors
Presenter: Ilaria Attili
Session: Poster Display session 3
Resources:
Abstract