BRAF V600R

P2, N=26, Active, not recruiting, University Health Network, Toronto | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

Dabrafenib and trametinib would offer a new therapeutic option for rare cancers, such as high-grade gliomas, biliary tract cancer, and thyroid cancer. This study was funded by the Japan Agency for Medical Research and Development (22ck0106622h0003) and a Health and Labour Sciences Research Grant (19EA1008).

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Oct 2023 --> Apr 2025

P2, N=26, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024 | Recruiting --> Active, not recruiting

The Idylla BRAF Mutation Assay is a highly reliable and sensitive platform for detecting BRAF pathogenic variants in codon 600 in malignant melanoma. The test can be performed in less than two hours, significantly improving turnaround time, thus allowing faster time to treatment.

P=N/A, N=3, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Oct 2024 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Jul 2023; low accrual and lack of funds

P=N/A, N=8, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2024 --> Oct 2024 | Trial primary completion date: May 2023 --> Oct 2023

A complex of methods for determination of the nucleotide sequence of the BRAF codons 592-601 and the algorithm for testing samples and analyzing mutations in the BRAF codons 600-601 was developed. The method provides sufficient sensitivity to detect frequent mutations in codons 600 and 601 and allows them to be precisely differentiated.

P2/3, N=8, Terminated, The Christie NHS Foundation Trust | N=1050 --> 8 | Trial completion date: Oct 2030 --> Jan 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2030 --> Jan 2023; Closed earlier than expected due to the need for a redesign to reflect the recent change in standard of care guidelines. New design will include these treatments.

Rare BRAF mutations are not anecdotal in the metastatic melanoma population. Although data interpretation must remain careful owing to the limited size of some subsets of patients, non-E/K V600 BRAF mutations seem to confer a high sensitivity to targeted therapy, whereas MAPKis seem less effective in patients with non-V600 BRAF mutations. However, this strategy may be used as an alternative option in the case of immunotherapy failure in the latter population.

Four patients received combined BRAF/MEK inhibitors, two patients BRAF inhibitor monotherapy, and six patients were treated with ICI for advanced melanoma; four patients received adjuvant treatment with nivolumab. Given the few cases and the absence of randomized clinical trials, it is important to report clinical experiences, which can guide physicians in the treatment of melanomas harboring rare BRAF mutations.