A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations

NCT05503797 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: F8394-2012024-513578-23-002022-000627-20
• Study Type: interventional
• Target: 254
• Locations: 11 countries
• Sites: 66

Brief Summary

The objective of this Master Protocol is to evaluate the efficacy and safety of plixorafenib in participants with locally advanced or metastatic solid tumors, or recurrent or progressive primary central nervous system (CNS) tumors harboring BRAF fusions, or in participants with rare BRAF V600-mutated solid tumors, melanoma, thyroid, or recurrent primary CNS tumors.

Conditions

Cancer Harboring BRAF Alterations; HGG; LGG; Solid Tumors

Keywords

BRAF alterations; BRAF Fusions; BRAF V600E; BRAF Class 1; BRAF Class 2; High grade glioma; low grade glioma; HGG; LGG; Solid tumors

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) (Subprotocols A, B and C)

  ORR will be determined by standard tumor response criteria by blinded independent central review (BICR).

  Up to approximately 4 years

• Pharmacokinetics (Subprotocol D)

  Systemic exposure of plixorafenib measured by Cmax and AUC

  Up to approximately 4 years

Secondary Outcomes (13)

• Duration of Response (DOR) by BICR (Subprotocols A, B and C)

  Up to approximately 4 years

• ORR per Investigator Assessment

  Up to approximately 4 years

• DOR per Investigator Assessment

  Up to approximately 4 years

• Percentage of Participants with DOR at 6 months, 12 months, and 18 months

  6 months, 12 months and 18 months

• Time to Response by BICR (Subprotocols A, B and C)

  Up to approximately 4 years

Study Arms (4)

Subprotocol A

EXPERIMENTAL

Participants with unresectable, locally advanced or metastatic solid tumors or primary CNS tumors harboring BRAF fusions will receive plixorafenib which will be increased as tolerated, continuously in 3-week cycles until disease progression, unacceptable toxicity, or other reason for withdrawal.

Drug: Plixorafenib

Subprotocol B

EXPERIMENTAL

Participants with recurrent primary CNS tumors harboring BRAF V600E mutations will receive plixorafenib, continuously in 3-week cycles until disease progression, unacceptable toxicity, or other reason for withdrawal.

Drug: Plixorafenib

Subprotocol C

EXPERIMENTAL

Participants with advanced, rare, non-CNS solid tumors harboring BRAF V600E mutations will receive plixorafenib, continuously in 3-week cycles until disease progression, unacceptable toxicity, or other reason for withdrawal.

Drug: Plixorafenib

Subprotocol D

EXPERIMENTAL

Participants with BRAF V600E-mutated advanced solid tumors will receive plixorafenib until disease progression, unacceptable toxicity, or other reason for withdrawal.

Drug: Plixorafenib

Interventions

Plixorafenib DRUG

Oral tablets

Also known as: FORE8394, PLX8394

Subprotocol A; Subprotocol B; Subprotocol C; Subprotocol D

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subprotocol A:
• Male and female, ≥10 years of age, and weighing ≥30 kg.
• Histologic diagnosis of a solid tumor or primary CNS tumor.
• Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing.
• Have an archival tissue sample available meeting protocol requirements.
• Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
• Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.
• All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.
• Subprotocol B:
• Male and female, ≥10 years of age, and weighing ≥30 kg.
• Histological diagnosis of a primary CNS tumor, including but not limited to the following:
• 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
• 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.
• 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

You may not qualify if:

• Subprotocol A:
• Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease.
• Prior treatment with a MEK inhibitor.
• Malignancy with co-occurring activating RAS mutation(s) at any time.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• HIV infection with exceptions; discuss with treating physician.
• 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).
• Subprotocol B:
• Prior treatment with BRAF, ERK, and/or MEK inhibitor(s).
• Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• Active infection requiring systemic therapy.
• HIV infection with exceptions; discuss with treating physician.
• 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).
• Subprotocol C:

Sponsors & Collaborators

• Fore Biotherapeutics: lead

Study Sites (66)

Precision NextGen Oncology & Research Center

Beverly Hills, California, 90210, United States

RECRUITING

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

RECRUITING

University of California Los Angeles Rheumatology

Westwood, Los Angeles, California, 90095-6984, United States

RECRUITING

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

RECRUITING

University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

RECRUITING

The John Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Maryland Oncology Hematology- Columbia

Rockville, Maryland, 20850, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

St. Luke's Hospital

Duluth, Minnesota, 55805, United States

RECRUITING

Mosaic Life Care at Saint Joseph - Medical Center

Saint Joseph, Missouri, 64506, United States

RECRUITING

Nebraska Cancer Specialists - Midwest Cancer Center - Legacy

Omaha, Nebraska, 68130, United States

RECRUITING

Overlook Medical Center

Summit, New Jersey, 07901, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Atrium Health Wake Forest Baptist - Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

RECRUITING

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

COMPLETED

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Lifespan Cancer Institute - Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

SCRI - TriStar Medical Group Children's Specialists

Nashville, Tennessee, 37203, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Baylor Scott & White Research Institute

Dallas, Texas, 75246, United States

RECRUITING

Baylor Scott & White Medical Center

Temple, Texas, 43205, United States

RECRUITING

University of Washington School of Medicine

Seattle, Washington, 98109, United States

RECRUITING

West Virginia University Health Sciences Campus

Morgantown, West Virginia, 26506, United States

RECRUITING

Newcastle Private Hospital

New Lambton Heights, New South Wales, 2305, Australia

ACTIVE NOT RECRUITING

Orange Health Service

Orange, New South Wales, 2800, Australia

NOT YET RECRUITING

Sydney Children's Hospital Network - Randwick

Randwick, New South Wales, 2031, Australia

NOT YET RECRUITING

The Alfred

Melbourne, Victoria, 3004, Australia

RECRUITING

Sunny brook Health Sciences Centre- Bayview Campus

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Institut Bergonie

Bordeaux, Aquitaine, 33000, France

RECRUITING

Hôpital Nord de Marseille

Marseille, Bouches-du-Rhône, 13005, France

RECRUITING

Hôpital Morvan

Brest, Finistère, 29200, France

RECRUITING

Institut de Cancerologie de l'Ouest- Angers

Angers, Pays de la Loire Region, 49055, France

RECRUITING

Gustave Roussy

Villejuif, Val-de-Marne, 94805, France

RECRUITING

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, 31059, France

RECRUITING

Hôpital Universitaire Pitié Salpêtrière

Paris, Île-de-France Region, 75013, France

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Krankenhaus Nordwest

Frankfurt am Main, Hesse, 60488, Germany

ACTIVE NOT RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST

Meldola, Forli-Cesena, 47014, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, Naples, 80131, Italy

RECRUITING

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Haukeland Univeritetssjukehus

Bergen, Hordaland, 5021, Norway

NOT YET RECRUITING

Oslo Universitetssykehus-Radiumhospitalet

Oslo, 0379, Norway

NOT YET RECRUITING

Catholic University of Korea Saint Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Seoul National University Hospital

Suwon, Gyeonggido, 443-721, South Korea

RECRUITING

Dong-A University Hospital

Pusan, Gyeongsangnam-do, 602-812, South Korea

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul Teugbyeoisi, 03080, South Korea

RECRUITING

Severance Hospital

Seoul, Seoul Teugbyeolsi, 03722, South Korea

RECRUITING

Hospital Clinico Universitarlo de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

RECRUITING

Hospital Clinico Universitarlo de Valencia

Valencia, Valencia, 46010, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesús

Madrid, 28009, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Skånes Universitetssjukhus

Lund, Skåne County, 221 85, Sweden

RECRUITING

Karolinska Universitetssjukhuset

Solna, Stockholm County, 171 64, Sweden

RECRUITING

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

RECRUITING

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Glioma

Interventions

PLX8394

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Jessica Rine

CONTACT

610-442-4517; jessica.rine@fore.bio

Geri Bardelli

CONTACT

978-835-2310; geraldine.bardelli@fore.bio

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All four open-label single-arm subprotocols will enroll patients independently of one another, in parallel.

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: August 17, 2022
• Study Start: February 21, 2023
• Primary Completion (Estimated): June 27, 2026
• Study Completion (Estimated): December 28, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Starting 6 months after publication of summary data and ending 36 months following article publication.
• Access Criteria: Qualified external researchers may submit a request to access deidentified patient-level data and related study documents (eg. study protocol). These requests will be reviewed and approved by an independent committee on the basis of scientific merit and may be subject to certain criteria, conditions, and exceptions. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

Locations

DE (3); FR (7); AU (4); KR (6); CA (2); GB (2); ES (6); US (28); SE (2); IT (4); NO (2)