Actively Recruiting

Phase 2
Age: 10Years +
All Genders
ID05503797

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

Led by Fore Biotherapeutics · Updated on 2026-06-05

254

Participants Needed

70

Research Sites

26 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating the safety and effectiveness of plixorafenib in people with advanced or metastatic solid tumors, including primary central nervous system tumors, that have specific BRAF gene alterations. The study focuses on participants with BRAF fusions or rare BRAF V600 mutations in tumors like melanoma, thyroid cancer, or recurrent CNS tumors. This is a Phase 2 trial aiming to understand how well plixorafenib works in these cancer types. Participants receive plixorafenib as oral tablets continuously in 3-week cycles. The dose may be increased as tolerated and treatment continues until the disease progresses, unacceptable side effects occur, or other reasons lead to stopping. The study includes different groups based on tumor types and BRAF mutation status, including unresectable solid or CNS tumors with BRAF fusions, recurrent CNS tumors with BRAF V600E mutations, and advanced rare non-CNS solid tumors with BRAF V600E mutations. During the trial, participants will have scans and tests before starting treatment to assess tumor changes. Researchers will monitor tumor response, duration of response, progression-free survival, overall survival, and treatment side effects for up to four years. Blood samples will be taken to study how the drug is processed in the body. Participants will be closely followed throughout the study to evaluate the drug's effects and safety.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 10Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Male or female participants aged 10 years or older and weighing at least 30 kg
  • Histologic diagnosis of a solid tumor or primary central nervous system tumor
  • Documented BRAF gene fusion or BRAF V600E mutation detected by validated genetic testing
  • Availability of an archival tissue sample meeting protocol requirements
  • Consent to provide scans before baseline to assess tumor changes
  • Have received all available standard therapies, are intolerant to standard therapies, or treatment with standard therapy is not appropriate
  • All side effects from prior treatments must have resolved to Grade 1 or baseline
  • Measurable disease as determined by imaging or physical exam (for applicable subprotocols)
  • Willingness to comply with study procedures including biopsies and ECG substudy (for specific subprotocols)
Not Eligible

You will not qualify if you...

  • Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations or MEK inhibitors (specific to some subprotocols)
  • Presence of malignancies with co-occurring activating RAS mutations
  • Uncontrolled illness that limits compliance with study requirements
  • HIV infection with exceptions as discussed with treating physician
  • Gastrointestinal conditions that affect absorption of oral plixorafenib
  • Grade 2 or higher liver enzyme changes attributed to prior immune checkpoint inhibitor treatment
  • Known or suspected neurofibromatosis-1 or RAS related gene alterations
  • Active infection requiring systemic therapy
  • Presence of CNS metastases (for specific subprotocols)
  • Use or anticipated need for medications that prolong QT interval or history of significant heart conditions
  • Hypertension with systolic blood pressure over 160 mm Hg or significant ECG abnormalities

AI-Screening

AI-Powered Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Repeated 3-week cycles until disease progression or discontinuation

Participants receive plixorafenib orally in repeated 3-week cycles. Treatment continues until disease progression, unacceptable toxicity, or other reasons for withdrawal.

Visits occur regularly during treatment cycles as per protocol

Trial Site Locations

Total: 70 locations

1

Precision NextGen Oncology & Research Center

Beverly Hills, California, United States, 90210

Actively Recruiting

2

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94143

Actively Recruiting

3

University of California Los Angeles Rheumatology

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

Actively Recruiting

4

Norwalk Hospital

Norwalk, Connecticut, United States, 06856

Actively Recruiting

5

University of Miami Hospital and Clinics

Miami, Florida, United States, 33136

Actively Recruiting

6

The John Hopkins Hospital

Baltimore, Maryland, United States, 21287

Actively Recruiting

7

Maryland Oncology Hematology- Columbia

Rockville, Maryland, United States, 20850

Actively Recruiting

8

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Actively Recruiting

9

Massachusetts General Hospital

Boston, Massachusetts, United States, 02214

Actively Recruiting

10

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Not Yet Recruiting

11

St. Luke's Hospital

Duluth, Minnesota, United States, 55805

Actively Recruiting

12

Mosaic Life Care at Saint Joseph - Medical Center

Saint Joseph, Missouri, United States, 64506

Actively Recruiting

13

Nebraska Cancer Specialists - Midwest Cancer Center - Legacy

Omaha, Nebraska, United States, 68130

Actively Recruiting

14

Overlook Medical Center

Summit, New Jersey, United States, 07901

Actively Recruiting

15

Columbia University Irving Medical Center

New York, New York, United States, 10032

Actively Recruiting

16

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Actively Recruiting

17

Atrium Health Wake Forest Baptist - Comprehensive Cancer Center

Winston-Salem, North Carolina, United States, 27157

Actively Recruiting

18

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

Actively Recruiting

19

The Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States, 43221

Actively Recruiting

20

Taylor Cancer Research Center

Maumee, Ohio, United States, 43537

Actively Recruiting

21

Toledo Clinic Cancer Center

Toledo, Ohio, United States, 43623

Completed

22

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Actively Recruiting

23

Lifespan Cancer Institute - Rhode Island Hospital

Providence, Rhode Island, United States, 02903

Actively Recruiting

24

SCRI - TriStar Medical Group Children's Specialists

Nashville, Tennessee, United States, 37203

Actively Recruiting

25

SCRI Oncology Partners

Nashville, Tennessee, United States, 37203

Actively Recruiting

26

Baylor Scott & White Research Institute

Dallas, Texas, United States, 75246

Actively Recruiting

27

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Actively Recruiting

28

Baylor Scott & White Medical Center

Temple, Texas, United States, 43205

Actively Recruiting

29

University of Washington School of Medicine

Seattle, Washington, United States, 98109

Actively Recruiting

30

West Virginia University Health Sciences Campus

Morgantown, West Virginia, United States, 26506

Actively Recruiting

31

Newcastle Private Hospital

New Lambton Heights, New South Wales, Australia, 2305

Actively Recruiting

32

Orange Health Service

Orange, New South Wales, Australia, 2800

Actively Recruiting

33

Sydney Children's Hospital Network - Randwick

Randwick, New South Wales, Australia, 2031

Actively Recruiting

34

Flinders Medical Centre

Bedford Park, South Australia, Australia, 5042

Actively Recruiting

35

The Alfred

Melbourne, Victoria, Australia, 3004

Actively Recruiting

36

Sunny brook Health Sciences Centre- Bayview Campus

Toronto, Ontario, Canada, M4N 3M5

Actively Recruiting

37

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada, H3T 1C5

Actively Recruiting

38

Institut Bergonie

Bordeaux, Aquitaine, France, 33000

Actively Recruiting

39

Hôpital Nord de Marseille

Marseille, Bouches-du-Rhône, France, 13005

Actively Recruiting

40

Hôpital Morvan

Brest, Finistère, France, 29200

Actively Recruiting

41

Institut de Cancerologie de l'Ouest- Angers

Angers, Pays de la Loire Region, France, 49055

Actively Recruiting

42

Gustave Roussy

Villejuif, Val-de-Marne, France, 94805

Actively Recruiting

43

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, France, 31059

Actively Recruiting

44

Hôpital Universitaire Pitié Salpêtrière

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

Actively Recruiting

45

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany, 69120

Actively Recruiting

46

Krankenhaus Nordwest

Frankfurt am Main, Hesse, Germany, 60488

Active, Not Recruiting

47

Charité - Universitätsmedizin Berlin

Berlin, Germany, 13353

Actively Recruiting

48

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

Meldola, Forli-Cesena, Italy, 47014

Actively Recruiting

49

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, Naples, Italy, 80131

Actively Recruiting

50

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

Milan, Italy, 20132

Actively Recruiting

51

Istituto Europeo di Oncologia

Milan, Italy, 20141

Actively Recruiting

52

Erasmus Medisch Centrum

Rotterdam, South Holland, Netherlands, 3015 GD

Actively Recruiting

53

Haukeland Univeritetssjukehus

Bergen, Hordaland, Norway, 5021

Actively Recruiting

54

Oslo Universitetssykehus-Radiumhospitalet

Oslo, Norway, 0379

Actively Recruiting

55

Catholic University of Korea Saint Vincent's Hospital

Suwon, Gyeonggi-do, South Korea, 16247

Actively Recruiting

56

Seoul National University Hospital

Suwon, Gyeonggido, South Korea, 443-721

Actively Recruiting

57

Dong-A University Hospital

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

Actively Recruiting

58

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea, 58128

Actively Recruiting

59

Seoul National University Hospital

Seoul, Seoul Teugbyeoisi, South Korea, 03080

Actively Recruiting

60

Severance Hospital

Seoul, Seoul Teugbyeolsi, South Korea, 03722

Actively Recruiting

61

Hospital Clinico Universitarlo de Santiago

Santiago de Compostela, A Coruña, Spain, 15706

Actively Recruiting

62

Hospital Clinico Universitarlo de Valencia

Valencia, Valencia, Spain, 46010

Actively Recruiting

63

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Actively Recruiting

64

Hospital Infantil Universitario Niño Jesús

Madrid, Spain, 28009

Actively Recruiting

65

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Actively Recruiting

66

Hospital Universitario Virgen del Rocío

Seville, Spain, 41013

Actively Recruiting

67

Skånes Universitetssjukhus

Lund, Skåne County, Sweden, 221 85

Actively Recruiting

68

Karolinska Universitetssjukhuset

Solna, Stockholm County, Sweden, 171 64

Actively Recruiting

69

The Christie NHS Foundation Trust

Manchester, England, United Kingdom, M20 4BX

Actively Recruiting

70

Sarah Cannon Research Institute

London, United Kingdom, W1G 6AD

Actively Recruiting

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Research Team

J

Jessica Rine

G

Geri Bardelli

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

4

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