Reference Detail


Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at :

Ref Type abstract
Authors E.J. Sherman, F. Tsai, F. Janku, C. Allen, R. Yaeger, N. Ammakkanavar, N. Butowski, G. Michelson, M. Paz, A. Tussay-Lindenberg, K. Wang, S. Shepherd, E. Dehan, M. de la Fuente, J. Rodon
Title 466P Efficacy of BRAF inhibitor FORE8394 in BRAF V600+ patients
Abstract Text Abstract 466P Background FORE8394 is a selective, potent BRAFi (class 1, 2 including fusions). By disrupting BRAF dimers, FORE8394 evades paradoxical MAPK pathway activation and may be less prone to toxicities & resistance typical of 1st generation BRAFi. Methods This is an ongoing phase I/IIa single-arm, open label study in patients (pts) with advanced tumors with activating BRAF alterations to assess safety, PK, & efficacy in pts with ≥1 post baseline assessment (mITT). Pts received oral FORE8394 900-3600 mg/day alone or with cobicistat (CYP3A4/P-gp inhibitor) to increase exposure. The majority of FORE8394 doses were 450-900 mg BID. This interim analysis was in adults (≥18 yrs) with V600+ advanced solid & central nervous system (CNS) tumors. Results To date, 94 pts received ≥1 dose of FORE8394 (median age [range] 58 yr [4,86]). Median lines of therapy were 2 (0, 9). 10/94 have been on treatment for >2 yrs. Clinically relevant exposures were achieved, suggesting a wide therapeutic window. Symptomatic adverse events (AEs) were low grade. AEs (≥20%) were reversible hepatic lab changes (mainly in first 2 cycles), fatigue, nausea, diarrhea, & vomiting. AEs ≥Grade 3 (≥5%) were increased ALT (10.6%), increased bilirubin (6.4%), hyponatraemia (5.3%), with no secondary skin malignancies or acanthomas. 48 pts were V600+ (mITT), including 14 (29%) with colorectal cancer (CRC, 1 confirmed partial response [cPR]); 4/48 V600 K/M (0 cPR). Objective response rate (ORR) = 20.8%; clinical benefit rate (CBR) = 35.4% at 24 weeks. 19 pts with no prior BRAFi/MAPKi (excluding CRC) included: 6 papillary thyroid cancer (PTC), 4 anaplastic thyroid cancer (ATC), 3 high grade glioma (HGG), and others; 2/19 V600K/M (ATC, pancreas). cPR = 31.6% (6/19), CBR = 63.2% (12/19), median response time = 12.1 wks; median response duration = 13.5 mo. Of 6 BRAFi/MAPKi naive pts with V600+ PTC, median progression free survival (PFS) not reached (median follow-up 4.9 yrs); 4 received FORE8934 ≥2 yrs, including 1 cPR (PFS 6.3+ years). 2/3 ATC pts (BRAFi naive/V600E) were on FORE8394 >2 yrs: PFS 2.4 yrs (cPR, SOD -63%) & PFS 3.4 yrs (SD, SOD -28%). 3/3 pt with BRAFi naive/V600E HGG had cPR. Conclusions FORE8394 achieved clinically relevant exposures, low rate of symptomatic AEs, and high ORR & durable PFS in BRAFi/MAPKi naïve pts with BRAFV600 solid & CNS tumors. NCT02428712.


  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")


  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References