BRAF T599

EGFR gene mutations were found in 16 (29%) and KRAS or NRAS alterations in 8 (14%) of the 54 tumors analyzed. We described herein seven non-hotspot/novel variants in the BRAF gene, highlighting their potential role in expanding our understanding of FCDTC genetics.

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

However, the efficacy of dabrafenib + trametinib on non-V600E mutant NSCLC in clinical practice only exists in some case reports. Here, we report a case of NSCLC patient carrying BRAF ex15 p.T599dup, who showed a clinical response to the combined therapy of dabrafenib + trametinib.

Conclusion  This constitutes one of the few reports on comprehensive analysis of molecular alterations underlying melanomas in Indian patients. A larger sample size, with more extensive molecular markers, would yield additional information on the disease manifestation.

Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations.

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

He was addressed to Dabrafenib/Trametinib targeted therapy, showing an initial dramatic response. In parallel, in-silico ligand-based homology modeling was set up and performed on this and an additional B-RAF rare variant (p.A598_T599insV) to unveil and justify the success of the B-RAF inhibitory activity of Dabrafenib, showing that it could adeptly bind both these variants in a similar manner to how it binds and inhibits the V600E mutant. These findings open up the possibility of broadening the spectrum of BRAF inhibitor-sensitive mutations beyond mutations at codon V600, suggesting that B-RAF V600 WT melanomas should undergo more specific investigations before ruling out the possibility of targeted therapy.

Molecular profiling of liquid biopsies at baseline identified alterations that could impact on patient outcomes. Our data suggest that the presence of BRAF pathogenic variants may be a good prognostic factor in stage IV NSCLC patients treated with immunotherapy or chemo-immunotherapy, while pathogenic mutations in ERBB3 could be a biomarker of high risk of disease progression. Additional studies analyzing larger cohorts of patients are needed to clarify these hypotheses.

P1/2, N=37, Terminated, Haihe Biopharma Co., Ltd. | N=150 --> 37 | Trial completion date: Dec 2024 --> Mar 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Mar 2023; Sponsor business decision

P1/2, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2023 --> Feb 2024 | Trial primary completion date: Feb 2023 --> Feb 2024

Novel BRAF mutations and V600E were frequently detected in thyroid cancer of Libyan patients; this suggests a potential role of these novel mutations in carcinogenesis and in anti-EGFR therapy resistance.

P1/2, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=38 --> 17