BRAF V600M

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.

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.

Moreover, we identify a small-molecular ITCH activator which suppresses acquired MAPKi-resistance in vivo. Thus, MAPKi-induced PD-L1 accelerates resistance, and a PD-L1-degrading ITCH activator prolongs antitumor response.

In our retrospective study we found that among stage III BRAF-mutant patients monotherapy with aPD1 was the most common adjuvant treatment regimen. In some patients with stage III disease IFN-alfa is still given. More studies are needed to define best adjuvant treatment for BRAF mutant stage III melanoma pts.

Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

P2, N=26, Recruiting, University Health Network, Toronto | Trial completion date: Sep 2021 --> Dec 2023 | Trial primary completion date: Sep 2021 --> Dec 2023

Although the combination of palbociclib + fixed-dose vemurafenib did not allow an increased palbociclib dosage above 25mg, a significant clinical benefit was achieved in pretreated melanoma patients. An association between the transcriptomic data and clinical response was highlighted.

P2, N=26, Recruiting, University Health Network, Toronto | Active, not recruiting --> Recruiting

P2, N=26, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting

No BRAF exon 15 mutations were identified in samples adjacent to PTCs that were BRAF WT. A mutagenic process affecting BRAF exon 15 occurs in a subset of thyroid glands that develop BRAF p.V600E mutated PTCs.