No new IRRs nor toxic deaths were reported. ENCO-PANI appears to be as safe and effective in pts treated for a BRAFm mCRC unable to continue CET and may represent a valid alternative therapeutic option in this setting.

P2, N=16, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting

P1, N=14, Active, not recruiting, Emory University | Trial completion date: Oct 2026 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2026

The patient was initially diagnosed with T4bN1bM1 and experienced disease progression following surgery and lenvatinib treatment. This possibility is supported by reliable evidence for the use of BRAF plus MEK inhibitor for brain metastasis from BRAF-mutated malignant melanoma. We conclude that encorafenib plus binimetinib treatment for brain metastasis from BRAF-mutated thyroid cancer is a safe and effective treatment choice.

BRAF V600E is associated with inferior prognoses compared to BRAF WT in early-stage CC. This finding will help optimize trial design for this population.

P1/2, N=38, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P2, N=24, Active, not recruiting, Providence Health & Services | Trial completion date: Oct 2027 --> Jan 2027 | Trial primary completion date: Oct 2025 --> Jan 2026

P2, N=98, Completed, Pfizer | Active, not recruiting --> Completed

P2, N=34, Not yet recruiting, Jinling Hospital, China

EST and Encorafenib (ECB as the internal standard) were differentiated using an isocratic mobile phase system on a reversed stationary phase (Eclipse Plus C18) column. In silico data proposed that minor structural modifications to the dichlorophenyl moiety or the piperazine ring during drug design may enhance the safety profile and metabolic stability relative to the properties of EST. Evaluating the EST metabolic stability and in silico ADME characteristics is essential for advancing innovative therapeutic research focused on improving metabolic stability.

Notably, the recent US Food and Drug Administration approval of the avutometinib/defactinib combination for KRAS-mutated recurrent LGSOC marks a significant milestone in targeted therapy for this disease. Despite these advances, challenges remain in optimizing sequencing strategies and overcoming acquired resistance. This review addresses the importance of understanding the distinct pathophysiology of LGSOC, diagnostic challenges, limitations of conventional treatments, and evolving therapeutic approaches in LGSOC.