Tafinlar (dabrafenib)

P2, N=16, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Dec 2025 --> Dec 2026

Using electrophilic probes, we show that treatment of BRAFV600E mutant melanoma cells with vemurafenib or trametinib decreases overall cysteine and lysine reactivity in BRAFV600E and MEK1/2, likely reflecting composite changes in amino acid accessibility across multiple reactive residues associated with inhibitor binding...Comparative analysis of ATP-competitive BRAFV600E inhibitors vemurafenib and dabrafenib indicated differences in aspartate and glutamate labeling patterns, consistent with the possibility that ABPP may detect inhibitor-associated variations in residue accessibility, which could reflect differences in inhibitor-bound conformations...Moreover, global proteome analyses of cysteine and lysine reactivity upon BRAFV600E inhibition revealed probe-accessible cysteine labeling changes on KSR2, suggesting a potential MAPK pathway remodeling. Together, these findings highlight ABPP as a valuable chemical biology approach for investigating inhibitor-dependent changes in kinase residue reactivity, offering a framework to investigate how kinase conformational dynamics and signaling pathway adaptation influence the therapeutic response and resistance in cancer.

In vivo studies demonstrated that combination therapy reduced tumor volume without causing systemic toxicity, accompanied by decreased proliferation markers (PCNA and Ki-67), increased apoptotic marker (cleaved caspase-3), and decreased B7-H3 expression in tumor tissues. These results suggest that JI-CJ002 may enhance the antitumor activity of dabrafenib, accompanied by modulation of oncogenic pathways.

In the absence of head-to-head trials comparing 1L nivolumab plus relatlimab (NIVO+RELA) to BRAF/MEK inhibitors, we compared its efficacy to dabrafenib+trametinib (DAB+TRAM), encorafenib+binimetinib (ENCO+BINI), vemurafenib+cobimetinib (VEM+COBI) and atezolizumab (ATEZO)+VEM+COBI using matching-adjusted indirect comparisons (MAICs)...These MAICs suggest that 1L dual IO therapy with NIVO+RELA confers a long-term OS advantage in BRAF-mutant advanced melanoma compared with BRAF/MEK inhibitor combinations despite lower ORR, consistent with prior evidence for 1L NIVO+IPI in this setting. As unanchored analyses, potential residual confounding remains, and results should be interpreted cautiously.

P1, N=6, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2026 --> Oct 2027 | Trial primary completion date: Feb 2026 --> Oct 2027

P2, N=49, Recruiting, Tianjin Medical University Cancer Institute and Hospital | Not yet recruiting --> Recruiting

Initially diagnosed with BRAF V600E-mutated melanoma, he received Dabrafenib and Trametinib...Despite initial treatment with Triptorelin, Docetaxel, and Abiraterone, disease progression occurred...This case illustrates the value of precision medicine and the role of liquid biopsy in guiding immunotherapy decisions for complex oncological cases. It supports the relevance of molecular profiling in selecting effective treatments beyond standard indications.

While dabrafenib and trametinib were well tolerated, treatment feasibility was restricted. These findings emphasize the urgent need for more robust research to identify effective therapeutic strategies for this molecular subgroup.

P4, N=100, Recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2030 --> Dec 2032 | Trial primary completion date: Dec 2029 --> Dec 2032

P2, N=49, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

Neoadjuvant therapy shows promise in improving resectability for unresectable and poorly differentiated thyroid cancers, with 51% of patients achieving R0 resection. Future studies should investigate optimal therapy selection, timing, dosing, and long-term outcomes, including disease-specific survival and patient-reported measures.