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
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract