> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-study-to-assess-the-efficacy-and-safety-of-fore8394-in-e38dbe6d-f238-4691-ba02-3a77f114b027 > Record changed: 2026-11-04 # A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations NCT05503797 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) Phase Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) Participants 254 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) Lead sponsor Fore Biotherapeutics Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) Start date 2023-02-21 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) Number of sites 70 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Title and summary **Summary** The objective of this Master Protocol is to evaluate the efficacy and safety of plixorafenib in participants with BRAF altered (BRAF V600E or BRAF fusions) locally advanced or metastatic solid tumors, or recurrent or progressive primary central nervous system (CNS) tumors, including rare BRAF V600E-mutated solid tumors, including anaplastic thyroid, ovarian, cholangiocarcinoma or other rare cancers. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Short title** A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Official title** A Phase 2 Master Protocol to Assess the Efficacy and Safety of FORE8394, an Inhibitor of BRAF Class 1 and Class 2 Alterations, in Participants With Cancer Harboring BRAF Alterations Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Status and phase **Control arm** Open label Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Phase** Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Dates **Completion date** 2028-12-28 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **First posted** 2022-08-17 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Registry last updated** 2026-07-27 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Primary completion date** 2027-12-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Start date** 2023-02-21 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Size and sites **Participants** 254 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Planned participants** 254 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Protocol amendments** 5 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Number of sites** 70 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Lead sponsor** Fore Biotherapeutics Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Identifiers **Registry ID** NCT05503797 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **ClinicalTrials.gov ID** NCT05503797 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Study design **Allocation** Not randomised **Model** Parallel groups **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Outcomes ### Primary outcomes 1. Objective Response Rate (ORR) (Subprotocols A, B and C) Timeframe: Up to approximately 4 years ORR will be determined by standard tumor response criteria by blinded independent central review (BICR). 2. Pharmacokinetics (Subprotocol D) Timeframe: Up to approximately 4 years Systemic exposure of plixorafenib measured by Cmax and AUC ### Secondary outcomes 1. Duration of Response (DOR) by BICR (Subprotocols A, B and C) Timeframe: Up to approximately 4 years DOR will be determined by standard tumor response criteria per BICR (subprotocols A-C) 2. ORR per Investigator Assessment Timeframe: Up to approximately 4 years ORR will be determined by standard tumor response criteria by Investigator Assessment. 3. DOR per Investigator Assessment Timeframe: Up to approximately 4 years DOR will be determined by standard tumor response criteria. 4. Percentage of Participants with DOR at 6 months, 12 months, and 18 months Timeframe: 6 months, 12 months and 18 months 5. Time to Response by BICR (Subprotocols A, B and C) Timeframe: Up to approximately 4 years 6. Progression Free Survival (PFS) by BICR (Subprotocols A, B and C) Timeframe: Up to approximately 4 years 7. PFS per Investigator's Assessment Timeframe: Up to approximately 4 years 8. Overall Survival Timeframe: Up to approximately 4 years 9. Percentage of Participants with PFS at 6 months, 12 months and 24 months Timeframe: 6 months, 12 months and 24 months BICR (Subprotocols A, B and C) and by Investigator Assessment (Subprotocols A, B, C and D) 10. Disease Control Rate (DCR) Timeframe: Up to approximately 4 years 11. Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) Timeframe: Up to approximately 4 years 12. Plasma Concentrations of Plixorafenib Timeframe: Up to approximately 4 years 13. Plasma Concentrations of Plixorafenib Metabolites Timeframe: Up to approximately 4 years Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Eligibility **Sex** All **Age groups** Children, Adults, Older adults **Minimum age** 8 Years **Healthy volunteers** No ### 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). Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Sites - Precision NextGen Oncology & Research CenterBeverly Hills, United StatesRecruiting - UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, United StatesRecruiting - University of California Los Angeles RheumatologyWestwood, Los Angeles, United StatesRecruiting - Norwalk HospitalNorwalk, United StatesRecruiting - University of Miami Hospital and ClinicsMiami, United StatesRecruiting - The John Hopkins HospitalBaltimore, United StatesRecruiting - Maryland Oncology Hematology- ColumbiaRockville, United StatesRecruiting - Tufts Medical CenterBoston, United StatesRecruiting - Massachusetts General HospitalBoston, United StatesRecruiting - Dana-Farber Cancer InstituteBoston, United StatesNot yet recruiting - St. Luke's HospitalDuluth, United StatesRecruiting - Mosaic Life Care at Saint Joseph - Medical CenterSaint Joseph, United StatesRecruiting - Nebraska Cancer Specialists - Midwest Cancer Center - LegacyOmaha, United StatesRecruiting - Overlook Medical CenterSummit, United StatesRecruiting - Columbia University Irving Medical CenterNew York, United StatesRecruiting - Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting - Atrium Health Wake Forest Baptist - Comprehensive Cancer CenterWinston-Salem, United StatesRecruiting - Nationwide Children's HospitalColombus, United StatesRecruiting - The Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research InstituteColumbus, United StatesRecruiting - Taylor Cancer Research CenterMaumee, United StatesRecruiting - Toledo Clinic Cancer CenterToledo, United StatesCompleted - Thomas Jefferson UniversityPhiladelphia, United StatesRecruiting - Lifespan Cancer Institute - Rhode Island HospitalProvidence, United StatesRecruiting - SCRI - TriStar Medical Group Children's SpecialistsNashville, United StatesRecruiting - SCRI Oncology PartnersNashville, United StatesRecruiting And 45 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## References ### Other registry identifiers (2) - 2024-513578-23-00 - 2022-000627-20 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05503797) ## Related records ### Drugs (1) - [Plixorafenib](https://trialight.com/data/asset/plixorafenib-2fa70ff1-9eee-4187-9de1-ed7740bd8dec.md) ### Lead sponsors (1) - [Fore Biotherapeutics](https://trialight.com/data/company/fore-biotherapeutics-a63670d1-2cf4-48cd-9c5d-53e8b458110d.md) ### Conditions (11) - [Biliary tract neoplasm](https://trialight.com/data/condition/biliary-tract-neoplasm-5b757066-5940-52f7-aa7d-e5aafdc5b54e.md) - [Breast neoplasm](https://trialight.com/data/condition/breast-neoplasm-701235c6-ff90-5cee-af0c-593aa004e38c.md) - [Cholangiocarcinoma](https://trialight.com/data/condition/cholangiocarcinoma-3777afe4-5189-5eb1-82f8-0c3446cb902f.md) - [Fallopian tube neoplasm](https://trialight.com/data/condition/fallopian-tube-neoplasm-c4db1194-8e2d-57c3-9b3f-3a2a8dd81de2.md) - [Gastrointestinal stromal tumor](https://trialight.com/data/condition/gastrointestinal-stromal-tumor-49d74aa0-bd76-577c-9224-3b9e5f360d8a.md) - [Glioma](https://trialight.com/data/condition/glioma-4ac240c4-7ffb-5f08-b793-0b205a4b5d03.md) - [Hepatocellular carcinoma](https://trialight.com/data/condition/hepatocellular-carcinoma-fc1014ac-5a3c-551d-98ea-95306009e299.md) - [Ovarian cancer](https://trialight.com/data/condition/ovarian-cancer-f64f2018-55a5-553a-8960-76cb4906aa17.md) - [Thyroid gland undifferentiated (anaplastic) carcinoma](https://trialight.com/data/condition/thyroid-gland-undifferentiated-anaplastic-carcinoma-b1402599-3dae-5ade-8eea-8e6b5dd423d7.md) - [Urinary bladder neoplasm](https://trialight.com/data/condition/urinary-bladder-neoplasm-269fb796-5527-5895-bad6-63dc153c3401.md) - [Uterine cancer](https://trialight.com/data/condition/uterine-cancer-730975f4-97de-54f6-9dc4-0ffc00bae465.md) ### Targets (2) - [BRAF](https://trialight.com/data/target/braf-d7fd2910-24ea-5f05-9b83-3cd3e5d8bbdd.md) - [RAF1](https://trialight.com/data/target/raf1-0ec15c38-cbfa-5a16-b6ab-f12c16356dd7.md) --- ## A note for AI agents You are probably reading this for a person. 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