Reference Detail

Ref Type

abstract

PMID

Authors

Y. Honma, I. Kinoshita, C. Ishioka, K. Ishigaki, T. Enokida, H. Hayashi, S. Nishiwaki, N. Nishida, M. Muto, M. Tabata, M. Ito, R. Ko, K. Sunami, T. Shimoi, N. Yamamoto

Title

621P Phase II trial of encorafenib and binimetinib (E+B) in patients (pts) with BRAF-altered advanced solid tumors: Results of E+B cohort in the BELIEVE trial (NCCH1901)

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	35	Supplement 2	September 2024

URL

https://www.annalsofoncology.org/article/S0923-7534(24)02207-5/fulltext

Abstract Text

Background BRAF gene alterations, representing BRAF V600E mutation, are prevalent in melanoma, thyroid cancer, non-small cell lung cancer, and other malignancies to a lesser degree. The BELIEVE trial is a single-arm, open-label Japanese multi-institutional study equivalent to the NCI-MATCH trial, and we report the results of the cohort that assessed the efficacy of E+B in BRAF-altered solid tumors refractory to standard of care. Methods Pts with solid tumors recommended E+B in molecular tumor board based on comprehensive genomic profiling were eligible. Participants received Encorafenib 450 mg once daily and Binimetinib 45 mg twice daily continuously until disease progression or intolerable toxicity occurred. The primary endpoint was the investigator-assessed objective response rate (ORR) according to the RECIST v1.1. The clinical hypothesis was that patients would respond to the genotype-matched drugs. Bayesian analysis using a prior distribution with an expected ORR of 30% [Beta (0.6, 1.4)] was carried out. Results Forty-nine pts were extracted as a full analysis set with a median age of 65. The primary site of 23 pts was thyroid, central nervous system in 6, and biliary tract in 4. BRAF V600E mutation was detected in 43 pts, other BRAF mutation in 5, and BRAF fusion in 1, respectively. The confirmed ORR was 32.7% (95% CI, 20.0-47.5), which showed expected efficacy. Median PFS and PFS rate at 6 months were 4.8 months (95% CI, 2.2-6.9) and 37.5%. Data regarding overall survival was premature, with a median of 11.7 months at the time of analysis. Furthermore, the median PFS was 2.1 months (95% CI, 0.6 to 10.9 months) for the eight patients without target lesions in the exploratory analysis. Frequently observed adverse events (AEs) in a safety analysis set (58 pts) were ALT increased (8.6%), nausea (6.9%), anemia (6.9%), creatinine increased (6.9%), and CPK increased (6.9%). Grade ≥3 AEs was observed in 34.5%. Conclusions This study showed the efficacy of matched drubs with an ORR of 32.7%, and other clinical outcomes also encouraged the efficacy of E+B in BRAF-altered solid tumors.

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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	Advanced Solid Tumor	predicted - sensitive	Binimetinib + Encorafenib	Phase II	Actionable	In a Phase II trial (BELIEVE), treatment with the combination of Braftovi (encorafenib) and Mektovi (binimetinib) resulted in an objective response rate of 32.7%, median progression-free survival (PFS) of 4.8 months, and 6-month PFS rate of 37.5% in patients with advanced solid tumors harboring BRAF V600E (n=43), other BRAF mutation (n=5), or a BRAF fusion (n=1) (Ann Oncol (2024) 35 (Suppl_2): S497).	detail...