Reference Detail

Ref Type

Journal Article

PMID

(38446982)

Authors

Schreck KC, Strowd RE, Nabors LB, Ellingson BM, Chang M, Tan SK, Abdullaev Z, Turakulov R, Aldape K, Danda N, Desideri S, Fisher J, Iacoboni M, Surakus T, Rudek MA, Bettegowda C, Grossman SA, Ye X

Title

Response rate and molecular correlates to encorafenib and binimetinib in BRAF-V600E mutant high-grade glioma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research			2024 Mar 06		Clin Cancer Res

URL

Abstract Text

While fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600 mutated HGG.In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles. Eligible patients were required to have high-grade glioma or glioblastoma with a BRAF-V600E alteration that was recurrent following at least one line of therapy including radiation.Five patients enrolled between January 2020 and administrative termination in November 2021 (due to closure of the ABTC). Enrolled patients received treatment for 2-40 months; currently one patient remains on treatment. Centrally determined radiographic response rate was 60%, with one complete response and two partial responses. Methylation profiling revealed all tumors cluster most closely with anaplastic PXA. Transcriptional profile for MAPK-response signature was similar across all tumors at baseline and did not correlate with response in this small population. Circulating tumor DNA measured in plasma samples prior to treatment, during response, and upon progression showed feasibility of detection for the BRAF-V600E alteration. No new safety signal was detected.Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	high grade glioma	sensitive	Binimetinib + Encorafenib	Case Reports/Case Series	Actionable	In a Phase II trial, treatment with the combination of Mektovi (binimetinib) and Braftovi (encorafenib) demonstrated safety and activity in patients with high grade glioma harboring BRAF V600E, resulting in a radiographic response rate of 60% (3/5, 1 complete and 2 partial responses), with stable disease in 1 patient, a median duration of response of 10 months, a median progression-free survival of 9.4 months, and a median overall survival of 14.6 months (PMID: 38446982; NCT03973918).	38446982