New hope for hard-to-treat BRAF cancers: drug targets tumor drivers

NCT ID NCT05503797

Disease control Sponsor: Fore Biotherapeutics Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jul 28, 2026 · Updated 2 times

Summary

This study tests a drug called FORE8394 (plixorafenib) in people aged 10 and older whose cancers have specific BRAF gene changes. The goal is to see if the drug can shrink tumors or slow their growth. About 254 participants with advanced solid tumors or brain tumors will take the drug and be monitored for response and side effects.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 254 people

The number the study aims to enrol. It can still change while the study runs.

Started

Feb 2023

Expected to finish

Dec 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

8 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria Subprotocol A: 1. Male and female, ≥8 years of age, and weighing ≥25 kg. 2. Histologic diagnosis of a solid tumor or primary CNS tumor. 3. Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing. 4. Have an archival tissue sample available meeting protocol requirements. 5. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory. 6. Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate. 7. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline. Subprotocol B: 1. Male and female, ≥8 years of age, and weighing ≥25 kg. 2. Histological diagnosis of a primary CNS tumor, including but not limited to the following: 1. Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor (including glioblastoma, anaplastic astrocytoma, high grade astrocytoma with piloid features, pilocytic astrocytoma, gliosarcoma, anaplastic pleomorphic xanthoastrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, not otherwise specified \[NOS\], ganglioglioma, or recurrent LGG). OR 2. Pediatric patients (8-17 years of age) with a Grade 3 or 4 glioma or glioneuronal tumor, including those with a prior, histologically confirmed, diagnosis of a low-grade glioma or glioneuronal tumor and now have radiographic or histopathological findings consistent with WHO \[2021\] Grade 3 or 4 primary CNS tumor. 3. Participants must have unresectable, locally advanced or metastatic disease that: i. Had prior treatment with radiotherapy and/or first-line chemotherapy or concurrent chemoradiation therapy OR * Note: Participants who have a WHO Grade 3 or 4 glioma for whom chemotherapy and/or radiotherapy is not considered standard of care may remain eligible for the study. ii. Is intolerant to available therapies OR iii. The investigator has determined that treatment with standard therapy is not appropriate. 3. Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test at CLIA or CLIA-equivalent laboratory approved by sponsor or sponsor-designated central test. 4. An archival tissue sample available meeting protocol requirements, or fresh biopsy is required if the archival sample is not available for retrospective confirmation test. 5. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory. 6. Measurable disease based upon specified response criteria, as determined by the radiographic BICR. 7. All adverse events related to prior therapies (eg, chemotherapy, radiotherapy, surgery) must have resolved to Grade 1 or baseline. 8. Participants who are receiving corticosteroid treatment must be on a stable or decreasing dose of ≤8 mg/day of dexamethasone or equivalent corticosteroid treatment for 7 days prior to first dose of study treatments. Subprotocol C: 1. Male and female, ≥8 years of age, and weighing ≥25 kg. 2. Histologic diagnosis of a rare BRAF V600E-mutated solid tumor that is unresectable, locally advanced or metastatic. 3. Measurable disease on CT, MRI, or physical exam 4. Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test. 5. Have an archival tissue sample available meeting protocol requirements. 6. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory 7. Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate. Subprotocol D: 1. Male and female, ≥8 years of age, and weighing ≥25 kg. 2. Histologic diagnosis of a solid tumor harboring a BRAF V600E mutation and not eligible for other subprotocols. 3. Measurable disease on CT, MRI, or physical exam. 4. Evidence of BRAF V600E mutation in tumor and/or blood detected by genomic tests. 5. Consent to provide a tumor biopsy. 6. Willingness to comply with the ECG substudy procedures. 7. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline. Exclusion Criteria: Subprotocol A: 1. Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease. 2. Prior treatment with a MEK inhibitor. 3. Tyrosine kinase inhibitor(s) and/or targeted therapies are allowed (other than BRAF/MAPK pathway inhibitors per Exclusion Criteria 3 and 4) and will be restricted to no more than the number of lines of therapy that are consistent with standard treatment guidelines. 4. Malignancy with co-occurring activating RAS mutation(s) at any time. 5. Uncontrolled intercurrent illness that would limit compliance with study requirements. 6. HIV infection with exceptions; discuss with treating physician. 7. Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral plixorafenib or cobicistat (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, and small bowel resection). 8. Grade ≥2 changes in AST, ALT, GGT, or bilirubin attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if resolved. Subprotocol B: 1. Prior treatment with BRAF, ERK, and/or MEK inhibitor(s). 2. Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations. 3. Uncontrolled intercurrent illness that would limit compliance with study requirements. 4. Active infection requiring systemic therapy. 5. HIV infection with exceptions; discuss with treating physician. 6. Have impairment of GI function or GI disease that may significantly alter the absorption of oral plixorafenib (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 7. Grade ≥ 2 changes in AST, ALT, gamma-glutamyl transaminase (GGT), or bilirubin attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if resolved. Subprotocol C: 1. Diagnosis of colorectal adenocarcinoma or pancreatic ductal adenocarcinoma (neuroendocrine or acinar tumors are eligible). 2. Diagnosis of BRAF V600E-mutated cutaneous melanoma, papillary thyroid cancer, or NSCLC. 3. Participant has CNS metastases. 4. Prior treatment with BRAF, ERK, and/or MEK inhibitor(s), unless otherwise specified for specific tumor types (i.e. low grade serous or borderline ovarian cancer). 5. Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations. 6. Participants with prostate, breast, or gynecologic cancers with known activating mutations that lead to constitutive hormone receptor activation (AR-V7, ESR1). 7. Uncontrolled intercurrent illness that would limit compliance with study requirements. 8. Active infection requiring systemic therapy. 9. HIV infection with exceptions; discuss with treating physician. Subprotocol D: 1. Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations or other co-occurring driver mutations. 2. Participant has a non-CNS solid tumor with CNS metastases. 3. Uncontrolled intercurrent illness that would limit compliance with study requirements. 4. Active infection requiring systemic therapy. 5. HIV infection with exceptions; discuss with treating physician. 6. Use or anticipate the need for medications with known risk for QT-prolonging potential and Torsades de Pointes. 7. History of acute or chronic cardiovascular disease or surgery, hypertension, with systolic blood pressure \>160mm HG, history of QTc abnormalities, or clinical significantly ECG abnormalities (for participants in the ECG substudy).

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Conditions

The condition(s) this trial relates to.

Biliary Tract Neoplasms breast neoplasm cholangiocarcinoma fallopian tube neoplasm gastrointestinal stromal tumor glioma hepatocellular carcinoma ovarian cancer pediatric high-grade glioma T-cell large granular lymphocyte leukemia thyroid gland undifferentiated (anaplastic) carcinoma Urinary Bladder Neoplasms uterine cancer

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Cancer harboring BRAF alterations HGG LGG Solid tumors

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

68 sites in 12 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

Atrium Health Wake Forest Baptist - Comprehensive Cancer Center
RECRUITING

Winston-Salem, North Carolina, 27157, United States
Baylor Scott & White Medical Center
RECRUITING

Temple, Texas, 43205, United States
Baylor Scott & White Research Institute
RECRUITING

Dallas, Texas, 75246, United States
Catholic University of Korea Saint Vincent's Hospital
RECRUITING

Suwon, Gyeonggi-do, 16247, South Korea
Centre Hospitalier Universitaire Sainte-Justine
RECRUITING

Montreal, Quebec, H3T 1C5, Canada
Charité - Universitätsmedizin Berlin
RECRUITING

Berlin, 13353, Germany
Chonnam National University Hwasun Hospital
RECRUITING

Hwasun, Jeollanam-do, 58128, South Korea
Columbia University Irving Medical Center
RECRUITING

New York, New York, 10032, United States
Dana-Farber Cancer Institute
NOT_YET_RECRUITING

Boston, Massachusetts, 02215, United States
Dong-A University Hospital
RECRUITING

Pusan, Gyeongsangnam-do, 602-812, South Korea
Erasmus Medisch Centrum
RECRUITING

Rotterdam, South Holland, 3015 GD, Netherlands
Flinders Medical Centre
RECRUITING

Bedford Park, South Australia, 5042, Australia
Gustave Roussy
RECRUITING

Villejuif, Val-de-Marne, 94805, France
Haukeland Univeritetssjukehus
RECRUITING

Bergen, Hordaland, 5021, Norway
Hospital Clinico Universitarlo de Santiago
RECRUITING

Santiago de Compostela, A Coruña, 15706, Spain
Hospital Clinico Universitarlo de Valencia
RECRUITING

Valencia, Valencia, 46010, Spain
Hospital Infantil Universitario Niño Jesús
RECRUITING

Madrid, Madrid, 28009, Spain
Hospital Universitari Vall d'Hebron
RECRUITING

Barcelona, Barcelona, 08035, Spain
Hospital Universitario 12 de Octubre
RECRUITING

Madrid, Madrid, 28041, Spain
Hospital Universitario Virgen del Rocío
RECRUITING

Seville, Sevilla, 41013, Spain
Hôpital Morvan
RECRUITING

Brest, Finistère, 29200, France
Hôpital Nord de Marseille
RECRUITING

Marseille, Bouches-du-Rhône, 13005, France
Hôpital Universitaire Pitié Salpêtrière
RECRUITING

Paris, Île-de-France Region, 75013, France
Institut Bergonie
RECRUITING

Bordeaux, Aquitaine, 33000, France
Institut Universitaire du Cancer de Toulouse Oncopole
RECRUITING

Toulouse, 31059, France
Institut de Cancerologie de l'Ouest- Angers
RECRUITING

Angers, Pays de la Loire Region, 49055, France
Istituto Europeo di Oncologia
RECRUITING

Milan, 20141, Italy
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
RECRUITING

Naples, Naples, 80131, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
RECRUITING

Meldola, Forli-Cesena, 47014, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
RECRUITING

Milan, 20132, Italy
Karolinska Universitetssjukhuset
RECRUITING

Solna, Stockholm County, 171 64, Sweden
Krankenhaus Nordwest
ACTIVE_NOT_RECRUITING

Frankfurt am Main, Hesse, 60488, Germany
Lifespan Cancer Institute - Rhode Island Hospital
RECRUITING

Providence, Rhode Island, 02903, United States
Maryland Oncology Hematology- Columbia
RECRUITING

Rockville, Maryland, 20850, United States
Massachusetts General Hospital
RECRUITING

Boston, Massachusetts, 02214, United States
Memorial Sloan Kettering Cancer Center
RECRUITING

New York, New York, 10065, United States
Mosaic Life Care at Saint Joseph - Medical Center
RECRUITING

Saint Joseph, Missouri, 64506, United States
Nationwide Children's Hospital
RECRUITING

Colombus, Ohio, 43205, United States
Nebraska Cancer Specialists - Midwest Cancer Center - Legacy
RECRUITING

Omaha, Nebraska, 68130, United States
Newcastle Private Hospital
RECRUITING

New Lambton Heights, New South Wales, 2305, Australia
Norwalk Hospital
RECRUITING

Norwalk, Connecticut, 06856, United States
Orange Health Service
RECRUITING

Orange, New South Wales, 2800, Australia
Oslo Universitetssykehus-Radiumhospitalet
RECRUITING

Oslo, Oslo, 0379, Norway
Overlook Medical Center
RECRUITING

Summit, New Jersey, 07901, United States
Precision NextGen Oncology & Research Center
RECRUITING

Beverly Hills, California, 90210, United States
SCRI - TriStar Medical Group Children's Specialists
RECRUITING

Nashville, Tennessee, 37203, United States
SCRI Oncology Partners
RECRUITING

Nashville, Tennessee, 37203, United States
Sarah Cannon Research Institute
RECRUITING

London, W1G 6AD, United Kingdom
Seoul National University Hospital
RECRUITING

Suwon, Gyeonggido, 443-721, South Korea
Seoul National University Hospital
RECRUITING

Seoul, Seoul Teugbyeoisi, 03080, South Korea
Severance Hospital
RECRUITING

Seoul, Seoul Teugbyeolsi, 03722, South Korea
Skånes Universitetssjukhus
RECRUITING

Lund, Skåne County, 221 85, Sweden
St. Luke's Hospital
RECRUITING

Duluth, Minnesota, 55805, United States
Sunny brook Health Sciences Centre- Bayview Campus
RECRUITING

Toronto, Ontario, M4N 3M5, Canada
Sydney Children's Hospital Network - Randwick
RECRUITING

Randwick, New South Wales, 2031, Australia
Taylor Cancer Research Center
RECRUITING

Maumee, Ohio, 43537, United States
The Alfred
RECRUITING

Melbourne, Victoria, 3004, Australia
The Christie NHS Foundation Trust
RECRUITING

Manchester, England, M20 4BX, United Kingdom
The John Hopkins Hospital
RECRUITING

Baltimore, Maryland, 21287, United States
The Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute
RECRUITING

Columbus, Ohio, 43221, United States
Thomas Jefferson University
RECRUITING

Philadelphia, Pennsylvania, 19107, United States
Toledo Clinic Cancer Center
COMPLETED

Toledo, Ohio, 43623, United States
Tufts Medical Center
RECRUITING

Boston, Massachusetts, 02111, United States
UCSF Helen Diller Family Comprehensive Cancer Center
RECRUITING

San Francisco, California, 94143, United States
University of California Los Angeles Rheumatology
RECRUITING

Westwood, Los Angeles, California, 90095-6984, United States
University of Miami Hospital and Clinics
RECRUITING

Miami, Florida, 33136, United States
University of Texas MD Anderson Cancer Center
RECRUITING

Houston, Texas, 77030, United States
University of Washington School of Medicine
RECRUITING

Seattle, Washington, 98109, United States
Universitätsklinikum Heidelberg
RECRUITING

Heidelberg, Baden-Wurttemberg, 69120, Germany
West Virginia University Health Sciences Campus
RECRUITING

Morgantown, West Virginia, 26506, United States

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