FORE Biotherapeutics, a registration stage company dedicated to developing targeted therapies to treat patients with cancer, today announced that following the first of two pre-specified interim efficacy analyses for the FORTE basket study evaluating plixorafenib as a monotherapy in patients with advanced solid tumors with BRAF fusions, including recurrent or progressive primary central nervous system (CNS) tumors harboring BRAF fusions, the Independent Data Monitoring Committee (IDMC) has recommended that the study should continue as planned.
This first interim efficacy analysis for the BRAF fusion basket was conducted by the IDMC and was pre-specified to evaluate plixorafenib at a defined efficacy threshold after the first 25 participants treated in this basket of the FORTE study had sufficient data for response assessment, in addition to the IDMC’s ongoing oversight for safety. A second interim efficacy analysis is anticipated once sufficient data is available from 50 participants in this basket. The primary endpoint of overall response rate (ORR), supported by duration of response, in the FORTE BRAF fusions basket is being evaluated in approximately 75 patients.
“The passing of this first protocol-specified interim analysis for the BRAF fusion basket, and the second successful interim analysis in the FORTE study, is an important milestone and supports that tumor regressions continue to be observed, along with long duration of treatment, in patients treated with plixorafenib,” said Stacie Peacock Shepherd, M.D., Ph.D., Chief Medical Officer of Fore. “BRAF fusions are estimated to occur in approximately 1% of all solid tumors, yet there are no approved treatments for the vast majority of these patients and their prognosis remains extremely poor. BRAF fusions commonly occur in brain tumors, including in children and young adults, especially in low grade gliomas or rare glioneuronal tumors. Given plixorafenib’s novel dimer and paradox breaker mechanism of action that prevents MAPK activation, which supports the clinical activity and favorable tolerability being reported across several BRAF alterations and populations, we believe plixorafenib has the potential to become the first approved treatment option for the approximately 33,000 patients1 with BRAF fusions.”
William Hinshaw, Chief Executive Officer of Fore, commented, “Plixorafenib is emerging as a potential first-in-class and best-in-class next-generation BRAF inhibitor with a simple, once daily, oral dosing regimen without the PK booster cobicistat. At Fore Bio, we initiated studies in three areas of very high unmet need where we believe plixorafenib’s unique mechanism has the potential to add important clinical innovation and benefit for patients while getting to market as rapidly as possible, including in BRAF V600E central nervous system (CNS) tumors, BRAF fusions and rare BRAF V600E solid tumors. Plixorafenib has demonstrated activity across a wide number of tumors with BRAF alterations and has now passed two rigorous interim analyses, one for BRAF V600E CNS tumors and one for tumors with BRAF fusions, both encouraging milestones for the FORTE program. As we look ahead to the remainder of 2026 and into next year, we expect to achieve several important milestones, including reporting topline results from the BRAF V600E CNS basket around the end of 2026, submitting an NDA for the treatment of BRAF V600E CNS tumors during the first half of 2027, and reporting topline results from the BRAF fusion basket during the second half of 2027.”
Overview of Supporting Phase 1/2a BRAF Fusion Results2
In a Phase 1/2a study in adults with advanced solid tumors harboring BRAF fusions (n=14), plixorafenib achieved a 14% ORR, including one complete response (CR) and one partial response and 7 (50%) with stable disease, for a disease control rate of 64%. Both responders continue treatment under sIND with a total duration of over 8 years for the patient with CR and over 4 years for the patient with PR. Overall, plixorafenib was well tolerated with Grade 3 or higher adverse events attributed to plixorafenib occurring in less than 10% of the 113 participants. Plixorafenib demonstrated a manageable dermatologic safety profile with no related skin events leading to dose reduction, interruption, or treatment discontinuation. Discontinuation for adverse events related to plixorafenib was less than 2%.
About the Global Phase 2 FORTE Basket Study
The registration-intended FORTE Master Protocol is a global Phase 2 clinical trial which includes four baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are recurrent or progressive BRAF V600E primary CNS tumors, solid tumors with BRAF fusions and rare BRAF V600 mutated solid tumors. Plixorafenib is administered orally once daily (QD) with food as a monotherapy (no longer in combination with cobicistat). As part of the Bayesian adaptive design of the trial, interim efficacy analyses are conducted in each basket. The company previously reported a positive outcome from the BRAF V600 CNS basket in the third quarter of 2025. For the BRAF fusion basket, an additional interim efficacy analysis is anticipated once sufficient data is available from 50 participants. For the third basket of FORTE evaluating plixorafenib in rare BRAF V600 solid tumors, an interim efficacy analysis will be conducted after sufficient scans from approximately 25 patients are evaluated by the IDMC.
About Advanced Solid Tumors with BRAF Fusions
Solid tumors with BRAF fusions represent a high unmet medical need and a large development opportunity for plixorafenib. BRAF fusions occur in approximately 1% of all solid tumors, up to 2% of melanomas, and up to 4% of all brain gliomas. Limited treatment options are available, with approved therapies presenting limitations in tolerability and safety when administered.
About Plixorafenib
Plixorafenib is a novel BRAF inhibitor, with a unique mechanism of action that functions both as a dimer and paradox breaker, and that has demonstrated a differentiated and compelling monotherapy profile in clinical studies. Plixorafenib received Breakthrough Therapy Designation by the U.S. Food and Drug Administration in April 2026. In a previously conducted Phase 1/2 study in patients with MAPK inhibitor naïve BRAF V600 primary recurrent CNS tumors (n=9), plixorafenib monotherapy demonstrated an ORR of 67% and a clinical benefit rate of greater than 75%. In patients with V600 alterations who were MAPK inhibitor naïve, plixorafenib achieved a 42% response rate with prolonged duration of response (mDOR 17.8 months), with a clinical benefit rate of >70%. Plixorafenib also demonstrated a favorable safety and tolerability profile across tumor types, including relative to existing standard of care treatments for various BRAF altered tumors, with a discontinuation rate due to drug-related adverse events of less than 2%. Fore believes plixorafenib has the potential to overcome the limitations and tolerability challenges of currently available BRAF inhibitors, including high rates of rash, hemorrhage and growth effects in younger patients, through its unique mechanism of action targeting both BRAF Class I and Class II alterations, while avoiding the limitations of the earlier generation BRAF inhibitors that led to rapid recurrence of disease and the need for combination with a MEK inhibitor.
About FORE Biotherapeutics
Fore is a registration stage targeted oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394 or PLX-8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1st and 2nd generation BRAF inhibitors. For more information, please visit www.fore.bio or follow us on X and LinkedIn.
References
- Reflects Fore Bio’s 2034 estimates across G7 markets.
- Results presented at ASCO 2023 Annual Meeting and SNO 2023 Annual Meeting
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