FORE Biotherapeutics Announces Positive Outcome From a Planned Interim Efficacy Analysis for the FORTE Basket Study Evaluating Plixorafenib as a Monotherapy for Recurrent or Progressive BRAF V600 Primary CNS Tumors

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PHILADELPHIA--(BUSINESS WIRE)--Sep 24, 2025--

FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, today announced that following a pre-specified interim efficacy analysis for the Phase 2 FORTE basket study evaluating plixorafenib as a monotherapy in patients with recurrent or progressive BRAF V600-mutated primary central nervous system (CNS) tumors, the Independent Data Monitoring Committee (IDMC) has recommended that the study should continue as planned.

The interim efficacy analysis 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 had sufficient data for response assessment, in addition to the IDMC’s ongoing oversight for safety.

“We are very pleased that the BRAF V600 primary CNS basket of the FORTE study has passed the protocol-specified interim analysis supporting that tumor regressions in patients treated with plixorafenib continue to be observed,” said Stacie Peacock Shepherd, M.D., Ph.D., Chief Medical Officer of Fore. “We believe this is an encouraging development for the study, and more importantly, for patients in need of novel treatment options for recurrent primary CNS tumors. The data with this novel BRAF inhibitor, known as a paradox breaker, builds on the recent momentum for the potential of plixorafenib to benefit patients across BRAF-altered solid tumors, including the recent presentation of encouraging data in patients with BRAF-altered thyroid cancers, which has generated significant enthusiasm in the field. This significant milestone builds upon the validated approach of targeting BRAF, while avoiding the limitations of the earlier generation compounds that led to rapid recurrence of disease and the need for combination with a MEK inhibitor, and brings us one step closer to our objective of accelerating access to adults and children diagnosed with recurrent BRAF-altered brain or spinal cord tumors. We look forward to completing enrollment and reporting topline results from this registrational CNS basket in the second half of 2026.”

Macarena de la Fuente, M.D., Chief of Neuro-Oncology at the University of Miami Sylvester Comprehensive Cancer Center and lead CNS Investigator for both the Phase 1/2a and FORTE Phase 2 plixorafenib clinical studies, commented, “Primary CNS tumors can lead to significant disease and treatment-related morbidity, including neurocognitive deterioration and seizures, and premature death. The unique mechanism and tolerable safety profile seen in early clinical trials set plixorafenib apart from current limited treatments, including lower side effects of rash or fever and less risk of intratumoral bleeding, cardiac, ocular, or growth effects. The data that have been previously presented are very promising with durable clinical activity and favorable tolerability and we look forward to the full readout of data at the completion of this trial. We anticipate plixorafenib, with its unique mechanism of action, has the potential to transform the treatment paradigm for people with BRAF-altered recurrent or refractory primary CNS tumors.”

The primary endpoint of overall response rate (ORR), supported by duration of response, in the FORTE CNS basket is being evaluated in up to 50 patients with BRAF V600 primary recurrent CNS tumors.

About the Global Phase 2 FORTE Basket Study

The registration-intended FORTE Master Protocol is a global Phase 2 clinical trial which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are recurrent or progressive BRAF V600 primary CNS tumors, solid tumors with BRAF fusions and rare BRAF V600 mutated solid tumors. As part of the design of the trial, interim efficacy analyses will be conducted in the other two baskets of FORTE – the advanced solid tumors with BRAF fusions basket and the rare BRAF V600 solid tumors basket – after sufficient scans from approximately 25 patients in each basket are evaluated by the IDMC.

About BRAF Altered Recurrent Primary CNS Tumors

BRAF altered recurrent primary CNS tumors represent a high unmet medical need and a large market opportunity for plixorafenib. In the advanced treatment setting, patients are offered currently approved therapies, but those therapies have significant limitations in efficacy, tolerability, and safety.

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. 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%. 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 Bio believes plixorafenib has the potential to overcome the limitations of currently available BRAF inhibitors through its unique mechanism of action targeting BRAF, 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; formerly PLX8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1 st and 2 nd generation BRAF inhibitors. For more information, please visit www.fore.bio or follow us on X and LinkedIn.

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SOURCE: FORE Biotherapeutics

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PUB: 09/24/2025 08:00 AM/DISC: 09/24/2025 07:59 AM

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