FORE8394 for Cancer

Recruiting at 79 trial locations

Overseen By Geri Bardelli

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Fore Biotherapeutics

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: NF1, RAS mutations, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 4 years

254 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called plixorafenib (also known as FORE8394) for certain types of cancers. It targets tumors with specific gene changes called BRAF fusions or mutations, often found in advanced cancers like melanoma, thyroid cancer, and some brain tumors. The trial includes different groups for various cancer types, including those with tumors that have BRAF V600E mutations. Suitable candidates for this trial have advanced cancer with these specific mutations, have tried standard treatments without success, and are willing to provide tumor samples for testing. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take certain medications that strongly affect the liver enzyme CYP3A4, like some foods and herbal supplements (e.g., grapefruit, St. John's Wort). If you are on medications that interact with cobicistat, adjustments may be needed.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that plixorafenib, the treatment under study in this trial, has promising safety results. In earlier studies, participants tolerated plixorafenib well at various doses. Those with BRAF V600 mutations, which this treatment targets, responded well and experienced few severe side effects.

Another study found that plixorafenib specifically targets mutant BRAF proteins, linked to the cancers being studied. This focus helps protect healthy cells, potentially reducing side effects.

While plixorafenib remains under investigation, current research suggests it is generally safe for individuals with the specific types of cancer being targeted. However, like any treatment, risks exist, and discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Researchers are excited about plixorafenib because it targets BRAF mutations in a way that could offer new hope for patients with challenging cancers. Unlike traditional treatments such as chemotherapy or radiation, which can affect both healthy and cancerous cells, plixorafenib specifically targets BRAF V600E mutations and BRAF fusions found in various tumors. This precision in targeting means it has the potential to be more effective with fewer side effects. Additionally, plixorafenib is administered continuously in 3-week cycles, allowing for ongoing treatment adjustments based on patient tolerance and tumor response, which can optimize its effectiveness and improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that plixorafenib may help treat various cancers with BRAF mutations. In earlier studies, patients with a specific BRAF V600 mutation who had not previously received MAPKi treatment had a median progression-free survival (mPFS) of 64 months, living over five years without cancer progression. Additionally, 85.7% of these patients experienced a clinical benefit, with most seeing their condition improve or remain stable. The drug also caused significant tumor shrinkage in lab models of BRAF-mutated cancers, including brain tumors. In this trial, participants will receive plixorafenib in different subprotocols based on their specific cancer type and BRAF mutation. Plixorafenib blocks signals that help cancer cells grow, making it effective against tumors with certain BRAF mutations. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals aged 10 and older, weighing at least 30 kg, with certain types of advanced or recurrent cancer that have specific BRAF gene changes. They must have tried standard treatments or be unsuitable for them and should provide tissue samples for testing. People who've had prior MEK inhibitors or have uncontrolled illnesses are excluded.

Inclusion Criteria

Group A: Consent to provide scan(s) prior to baseline to assess change in tumor trajectory (at least 2 preferred). For participants with LGG, every effort should be made to provide 3 to 4 pre-baseline scans to the central imaging vendor whenever feasible

I have been diagnosed with a solid or primary brain tumor.

I can provide a recent tissue sample for the study, or I've never had targeted therapy if my sample is older.

Exclusion Criteria

I have NF1 or RAS-related mutations.

My cancer shows signs of changes due to past treatments, not because of a main mutation.

Group 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, Current or planned participation in a study of an investigational agent or device, Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral FORE8394 or cobicistat

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive plixorafenib, with or without cobicistat, in 3-week cycles until disease progression or unacceptable toxicity

Up to approximately 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FORE8394

Trial Overview The study tests the effectiveness of FORE8394 in patients with solid tumors or CNS tumors having BRAF alterations, as well as those with high-grade glioma (HGG) harboring a BRAF V600E mutation. It's an open-label trial divided into two parts based on different genetic mutations.

How Is the Trial Designed?

Group I: Subprotocol D Experimental Treatment 1 Intervention

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

Group II: Subprotocol C Experimental Treatment 1 Intervention

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.

Group III: Subprotocol B Experimental Treatment 1 Intervention

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.

Group IV: Subprotocol A Experimental Treatment 1 Intervention

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.

FORE8394 is already approved in United States for the following indications:

Approved in United States as Plixorafenib for:

• Primary Central Nervous System Tumors (PCNSTs) with BRAF V600 mutations

Who Is Running the Clinical Trial?

Fore Biotherapeutics

Lead Sponsor

Trials

8

Recruited

500+

Citations

1. fore.bio fore.bio/fore_biotherapeutics_presents_plixorafenib_data_ata_2025/

FORE Biotherapeutics Presents Phase 1/2a Plixorafenib ... Plixorafenib demonstrated mPFS of 64 months and a clinical benefit rate of 85.7% in patients with MAPKi-naïve BRAF V600-mutated papillary ...

2. aacrjournals.org aacrjournals.org/mct/article/24/10_Supplement/A073/766549/Abstract-A073-Plixorafenib-PLX8394-FORE8394

Abstract A073: Plixorafenib (PLX8394/FORE8394) treatment ... Plixorafenib (PLX8394/FORE8394) treatment leads to sustained tumor regression in preclinical models of BRAF-mutated primary and brain metastatic ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3006

Safety and efficacy of the novel BRAF inhibitor FORE8394 ... Conclusions: As single agent anticancer therapy, FORE8394 had antitumor activity in various tumors with BRAF alterations, including pts ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05503797

NCT05503797 | A Study to Assess the Efficacy and Safety ... Participants with recurrent primary CNS tumors harboring BRAF V600E mutations will receive plixorafenib, continuously in 3-week cycles until disease progression ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6404779/

RAF inhibitor PLX8394 selectively disrupts BRAF-dimers ... PLX8394 is a new RAF inhibitor that inhibits ERK signaling in tumors driven by BRAF V600 mutants and also in some models driven by dimer-dependent BRAF mutants ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05503797

NCT05503797 | A Study to Assess the Efficacy and Safety ... Participants with BRAF V600E-mutated advanced solid tumors will receive plixorafenib until disease progression, unacceptable toxicity, or other reason for ...

7. fore.bio fore.bio/wp-content/uploads/2024/04/Plixorafenib-Phase-1-2a-Oral-Presentation-ASCO-2023.pdf

Safety & Efficacy of the Novel BRAF Inhibitor FORE8394 in ... ➢ Specific activity against mutant BRAF in comparison to all wild type RAF proteins (including BRAF and CRAF). ➢ Targets mutated BRAF monomers and homodimers.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11372368/

A Next-Generation BRAF Inhibitor Overcomes Resistance to ... A brain-penetrant, selective, pan-mutant BRAF inhibitor could overcome resistance to approved BRAF inhibitors in BRAF-mutant cancers.

9. asco.org asco.org/abstracts-presentations/ABSTRACT488346

A phase 2 master protocol assessing plixorafenib for BRAF ... In a phase 1/2a study, plixorafenib demonstrated promising safety and clinical activity across a range of doses tested in tumors with BRAF V600 mutations or ...