A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations
Launched by FORE BIOTHERAPEUTICS · Aug 15, 2022
Trial Information
Current as of July 26, 2025
Recruiting
Keywords
ClinConnect Summary
This clinical trial is studying a new treatment called FORE8394 for people with certain types of cancer that have specific changes in the BRAF gene. The goal is to see how effective and safe this treatment is for patients who have locally advanced or metastatic solid tumors, as well as some types of brain tumors and rare cancers that have a specific mutation known as BRAF V600E. The trial is open to both children and adults aged 10 and older who meet certain health criteria and have already tried other standard treatments without success or are unable to tolerate them.
Participants in the trial will receive the new treatment and will be closely monitored to see how their cancer responds. They will also need to provide tissue samples to confirm their eligibility. It's important to know that patients should have recovered from any side effects of previous treatments before joining the trial. This study is currently recruiting participants, so if you or someone you know is interested, it may be worth discussing with a healthcare provider to see if they qualify.
Gender
ALL
Eligibility criteria
- • Inclusion Criteria
- Subprotocol A:
- • 1. Male and female, ≥10 years of age, and weighing ≥30 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, ≥10 years of age, and weighing ≥30 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 (10-17 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, ≥10 years of age, and weighing ≥30 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.
- • 8. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.
- Subprotocol D:
- • 1. Male and female, ≥10 years of age, and weighing ≥30 kg.
- • 2. Histologic diagnosis of a metastatic melanoma or thyroid cancer harboring a BRAF V600E mutation.
- • 3. Participants with cutaneous melanoma have previously received and not tolerated a BRAF inhibitor, while participants with thyroid cancer are MAPK inhibitor naïve.
- • 4. Measurable disease on CT, MRI, or physical exam.
- • 5. Evidence of BRAF V600E mutation in tumor and/or blood detected by genomic tests.
- • 6. Consent to provide a tumor biopsy.
- • 7. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.
- Exclusion Criteria:
- Subprotocol A:
- • 1. Participants with known co-occurring NF1 alteration and/or RAS-related mutations.
- • 2. Participants with evidence of subclonal mutations or heterogeneity that are indicative of a prior treatment effect instead of a driver mutation.
- • 3. Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease.
- • 4. Prior treatment with a MEK inhibitor.
- • 5. 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.
- • 6. Malignancy with co-occurring activating RAS mutation(s) at any time.
- • 7. Uncontrolled intercurrent illness that would limit compliance with study requirements.
- • 8. HIV infection with exceptions; discuss with treating physician.
- • 9. 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).
- • 10. Current active liver disease from any cause, including a positive test at screening for HBV (HBsAg), or HCV (HCV antibody, confirmed by HCV RNA PCR).
- • 11. 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 or cobicistat (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, thyroid cancer (ATC and PTC), or NSCLC.
- • 3. Participant has CNS metastases.
- • 4. Prior treatment with BRAF, ERK, and/or MEK inhibitor(s).
- • 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.
- • 2. Participants with known acquired driver mutations, including from prior MAPK pathway targeted therapies.
- • 3. Participant has CNS metastases.
- • 4. Uncontrolled intercurrent illness that would limit compliance with study requirements.
- • 5. Active infection requiring systemic therapy.
- • 6. HIV infection with exceptions; discuss with treating physician.
About Fore Biotherapeutics
Fore Biotherapeutics is a biopharmaceutical company dedicated to advancing innovative therapies that address significant unmet medical needs in oncology and rare diseases. With a strong focus on precision medicine, Fore Biotherapeutics leverages its proprietary drug development platform to identify and develop targeted treatments that improve patient outcomes. Committed to scientific excellence and collaboration, the company aims to transform the landscape of cancer care through its robust pipeline of novel biotherapeutics, fostering hope for patients and their families.
Contacts
Jennifer Cobb
Immunology at National Institute of Allergy and Infectious Diseases (NIAID)
Locations
Milano, , Italy
New York, New York, United States
Madrid, , Spain
Boston, Massachusetts, United States
San Francisco, California, United States
Duluth, Minnesota, United States
Boston, Massachusetts, United States
Seattle, Washington, United States
Columbus, Ohio, United States
Philadelphia, Pennsylvania, United States
Saint Joseph, Missouri, United States
New Lambton Heights, New South Wales, Australia
Berlin, , Germany
Melbourne, Victoria, Australia
Sevilla, , Spain
Paris, , France
Heidelberg, , Germany
Brest, , France
Seoul, , Korea, Republic Of
Baltimore, Maryland, United States
Miami, Florida, United States
Frankfurt, Hessen, Germany
Montréal, Quebec, Canada
San Francisco, California, United States
Summit, New Jersey, United States
Heidelberg, Baden Württemberg, Germany
New York, New York, United States
Manchester, , United Kingdom
Barcelona, , Spain
Lund, , Sweden
London, , United Kingdom
Villejuif, , France
Madrid, , Spain
Toledo, Ohio, United States
Solna, , Sweden
Hwasun, Jeollanam Do, Korea, Republic Of
Orange, New South Wales, Australia
Toulouse, , France
Dallas, Texas, United States
Providence, Rhode Island, United States
Morgantown, West Virginia, United States
Paris, Ile De France, France
Napoli, Naples, Italy
Brest, Finistère, France
Omaha, Nebraska, United States
Milan, , Italy
Suwon Si, Gyeonggi Do, Korea, Republic Of
Suwon, Gyeonggido [Kyonggi Do], Korea, Republic Of
Busan, Gyeongsangnam Do, Korea, Republic Of
Los Angeles, California, United States
Seoul, Seoul Teugbyeolsi, Korea, Republic Of
Santiago De Compostela, A Coruña, Spain
València, Valencia, Spain
Solna, Stockholms Län, Sweden
Meldola, Forli Cesena, Italy
Westwood, California, United States
Saint Joseph, Missouri, United States
Toronto, Ontario, Canada
Bordeaux Cedex, Aquitaine, France
Marseille, Bouches Du Rhône, France
Angers, Pays De La Loire, France
Lund, Skåne Län, Sweden
Temple, Texas, United States
Maumee, Ohio, United States
St Joseph, Missouri, United States
Colombus, Ohio, United States
Rockville, Maryland, United States
Randwick, , Australia
Suwon, Gyeonggido, Korea, Republic Of
Marseille, , France
Santiago De Compostela, , Spain
Randwick, New South Wales, Australia
Bergen, Hordaland, Norway
Oslo, , Norway
Patients applied
Timeline
First submit
Trial launched
Trial updated
Estimated completion
Not reported
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