FORE8394 Granted Fast Track Designation by FDA for Cancers With Class 1/2 BRAF Alterations

FORE8394, which received fast track designation by the FDA, is under ongoing evaluation in a phase 1/2a trial in patients with advanced solid and central nervous system tumors harboring BRAF alterations.

The FDA has granted fast track designation to the oral small molecule inhibitor FORE8394 as a treatment for patients with tumors harboring Class 1/2 BRAF alterations for whom all previous therapies have been exhausted, according to a press release from Fore Biotherapeutics.1

Data from a phase 1/2a study (NCT02428712) assessing FORE8394 in patients with solid and central nervous system tumors and activating BRAF V600 mutations read out at the 2022 European Society for Medical Oncology Congress.2 Investigators reported reaching clinically relevant exposures with FORE8394 in a population of 94 patients, which could be indicative of a wide therapeutic window. Moreover, confirmed responses and long-lasting benefit were observed across several tumor types.

In terms of safety, investigators noted that most symptomatic adverse effects (AEs) were low grade, most commonly including reversible alanine transaminase (ALT) increase (39.8%), aspartate aminotransferase (AST) increase (35.2%), fatigue (31.4%), nausea (26.9%), diarrhea (22.2%), and vomiting (20.4%). Grade 3 or higher AEs included ALT increase (14.8%), AST increase (2.8%), fatigue (0.9%), nausea (1.9%), diarrhea (3.7%), vomiting (0.9%), and bilirubin increase (6.5%).

“The FDA’s Fast Track Designation for FORE8394 underscores the urgent need faced by patients with advanced BRAF-muted cancers who have no other options,” Stacie Shepherd, MD, PhD, chief medical officer at Fore Biotherapeutics, said in a press release. “This designation will help us expedite our program as we advance toward our goal of addressing this area of high unmet need, including the anticipated initiation of our global phase 2 trial in the fourth quarter. We look forward to continuing to work closely with the FDA as we explore the potential for FORE8394 to improve outcomes for patients with these life-threatening cancers.”

Within the total patient population, primary tumors included colorectal cancer (CRC; 16.7%), papillary thyroid cancer (13.0%), and melanoma (13.9%). The majority of patients (91.3%) were treated at a dose of 900 mg to 1800 mg from once to 3 times a day.

Of 51 patients with BRAF V600–mutated disease, 3 patients with ovarian cancer —2 of whom received a prior BRAF inhibitor and MAPK-targeted regimen—achieved a partial response (PR); responses were ongoing at the time of the read out. Moreover, 1 patient with small bowel cancer who had been previously treated with a BRAF inhibitor achieved a PR. Within the CRC population (n = 14), 1 patient achieve a PR and another had stable disease for 28.6 months. In patients with high- and low-grade gliomas (n = 7), 6had PRs and 1 had stable disease for over 15 months. Additionally, in patients with papillary and anaplastic thyroid cancer, the median progression-free survival was not reached at a median follow-up of 5.6 years. Four patients remained on treatment for over 2 years.


  1. Fore Biotherapeutics announces fast track designation granted by FDA to FORE8394 for the treatment of cancers harboring BRAF class 1 and class 2 alterations. News release. Fore Biotherapeutics. September 28, 2022. Accessed September 29, 2022.
  2. Sherman EJ, Tsai F, Janku F, et al. Efficacy of BRAF inhibitor FORE8394 in BRAF V600+ patients. Ann Oncol. 2022;33(suppl 7):S197-S224. doi:10.1016/annonc/annonc1049