FORE8394 for Cancer

Recruiting at 60 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

250 Participants Needed

Trial Summary

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.

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Subprotocol D Experimental Treatment 2 Interventions

Participants with BRAF V600E-mutated cutaneous melanoma and BRAF V600E-mutated thyroid cancer (MAPK inhibitor naïve) will be randomized to receive plixorafenib with or without cobicistat.

Group II: Subprotocol C Experimental Treatment 2 Interventions

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

Group III: Subprotocol B Experimental Treatment 2 Interventions

Participants with recurrent primary CNS tumors harboring BRAF V600E mutations will receive plixorafenib administered with cobicistat, 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+