RECRUITING

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

Conditions

Cancer Harboring BRAF Alterations HGG LGG Solid Tumors Melanoma BRAF V600E/K Mutated Thyroid Cancer BRAF alterations BRAF Fusions BRAF V600E BRAF Class 1 BRAF Class 2 High grade glioma low grade glioma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-02-21

Study Completion:2026-12-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05503797

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:10 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	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. 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. 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. 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.

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

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.
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.
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.
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.

Contacts and Locations

Study Contact

Jessica Rine

CONTACT

610-442-4517

jessica.rine@fore.bio

Geri Bardelli

CONTACT

978-835-2310

geraldine.bardelli@fore.bio

Study Locations (Sites)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143

United States

University of California Los Angeles Rheumatology

Westwood, California, 90095-6984

United States

University of Miami Hospital and Clinics

Miami, Florida, 33136

United States

The John Hopkins Hospital

Baltimore, Maryland, 21287

United States

Maryland Oncology Hematology- Columbia

Rockville, Maryland, 20850

United States

Tufts Medical Center

Boston, Massachusetts, 02111

United States

St. Luke's Hospital

Duluth, Minnesota, 55805

United States

Mosaic Life Care at Saint Joseph - Medical Center

Saint Joseph, Missouri, 64506

United States

Nebraska Cancer Specialists - Midwest Cancer Center - Legacy

Omaha, Nebraska, 68130

United States

Overlook Medical Center

Summit, New Jersey, 07901

United States

Columbia University Irving Medical Center

New York, New York, 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Nationwide Children's Hospital

Columbus, Ohio, 43205

United States

Taylor Cancer Research Center

Maumee, Ohio, 43537

United States

Toledo Clinic Cancer Center

Toledo, Ohio, 43623

United States

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

United States

Lifespan Cancer Institute - Rhode Island Hospital

Providence, Rhode Island, 02903

United States

Baylor Scott & White Research Institute

Dallas, Texas, 75246

United States

Baylor Scott & White Medical Center

Temple, Texas, 43205

United States

University of Washington School of Medicine

Seattle, Washington, 98109

United States

West Virginia University Health Sciences Campus

Morgantown, West Virginia, 26506

United States

Collaborators and Investigators

Sponsor: Fore Biotherapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-02-21

Study Completion Date2026-12-28

Study Record Updates

Study Start Date2023-02-21

Study Completion Date2026-12-28

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Cancer Harboring BRAF Alterations
HGG
LGG
Solid Tumors
Melanoma BRAF V600E/K Mutated
Thyroid Cancer