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Search / Trial NCT05503797

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

Braf Alterations Braf Fusions Braf V600 E Braf Class 1 Braf Class 2 High Grade Glioma Low Grade Glioma Hgg Lgg Solid Tumors

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.

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

0 patients applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

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