A Study of FORE8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors

NCT ID: NCT02428712

Last Updated: 2025-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

113 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-30

Study Completion Date

2024-07-12

Brief Summary

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The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of FORE8394.

Detailed Description

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Dose Escalation (Part 1): To evaluate safety, pharmacokinetics, pharmacodynamics of FORE8394 in adult and pediatric patients with advanced BRAF- mutated tumors, and to identify the recommended Phase 2 Dose.

Dose Extension (Part 2): To access objective tumor response to FORE8394 treatment in adult and in adolescent patients with advanced BRAF- mutated tumors, to access RECIST, and to access pharmacokinetics, pharmacodynamics, and safety.

Conditions

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Advanced Unresectable Solid Tumors BRAF-mutated Tumors

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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FORE8394

Group A: Phase 1-Dose Escalation: Adult patients.

Group B: Phase 1-Dose Escalation: Pediatric patients.

Phase 2a-Dose Extension: Adult patients with advanced unresectable solid tumors will be enrolled among two cohorts.

* Cohort 1: Activating BRAF V600 mutations (glioma patients only)
* Cohort 2: Activating BRAF non-V600 mutations

Phase 2a-RP2D Confirmation: Adult patients.

Phase 2a-RP2D Redefinition and Extension:

* Cohort 3: Activating BRAF V600 or activating non-V600 mutation
* Cohort 4: Activating BRAF non-V600 mutations

Phase 2a-RP2D Redefinition:

* Cohort 6A: Advanced activating BRAF-mutated solid tumors
* Cohort 7A: Advanced activating BRAF-mutated solid tumors
* Cohort 8A: Advanced activating BRAF-mutated solid tumors

Group Type EXPERIMENTAL

FORE8394

Intervention Type DRUG

Interventions

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FORE8394

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 10 years and at least 30 kg.
* Phase 1-Dose Escalation (no longer enrolling as of Protocol Amendment 10): Patients with histologically confirmed advanced solid tumors who are refractory to, relapsed after, or intolerant to standard therapy or for whom no standard therapy exists.
* Phase 2a-Dose Extension: Criteria for Dose Extension \[HME\] Cohort 1 or Cohort 2, are specified below:

* Phase 2a-Dose Extension-Cohort 1

1. Patients with solid tumors (as of Amendment 10, only subjects with glioma tumors) driven by an activating BRAF-V600 mutation
2. Patients with no prior exposure to BRAF-directed therapy and for whom no standard therapy exists.
* Phase 2a-Dose Extension-Cohort 2

1. Patients with solid tumors driven by an activating BRAF non-V600 mutation, which can include a point mutation, gene amplification, fusion, insertion, or deletion
2. Participants with no prior exposure to BRAF-directed therapy and for whom no standard therapy exists.
* Phase 2a - RP2D Redefinition Extension: Following RP2D redefinition, extension participants must meet criteria for Cohort 3 or Cohort 4 as specified below:

1. Cohort 3: Participants with advanced unresectable gliomas driven by an activating BRAF V600 or activating non-V600 mutation who have no prior exposure to a BRAF, MEK, or ERK inhibitor and for whom no standard therapy exists.
2. Cohorts 4-8: Participants with advanced solid tumors driven by activating BRAF non V600 mutations, which can include a point mutation, gene amplification, fusion, insertion, deletion, or alternative splicing, who have no prior exposure to a BRAF, MEK, or ERK inhibitor.
* Measurable disease by RECIST 1.1.
* RANOS (CNS tumors) - High Grade Glioma for high grade glioma (Grades 3 and 4) and RANO-Low Grade Glioma for low grade glioma.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Adequate hematologic, hepatic, and renal function.
* Women of child-bearing potential must have a negative pregnancy test and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Women of non-child-bearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year.
* Fertile men must agree to use an effective method of birth control during the study and for up to 3 months after the last dose of study drug.
* Completion of previous anti-cancer therapy at least 2 weeks before study drug initiation.

Exclusion Criteria

* Participants with known co-occurring RAS-related mutations or RTK activation are not allowed.
* Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study.
* Uncontrolled intercurrent illness.
* Patients with colorectal cancer or pancreatic cancer
* Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor. Patients with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
* Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
* Clinically significant cardiac disease.
* Known infection with HIV, HBV, or HCV or a known carrier of HBV or HCV.
Minimum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fore Biotherapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stacie Peacock Shepherd, MD, PhD

Role: STUDY_CHAIR

Fore Biotherapeutics U.S. Inc.

Locations

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HonorHealth

Scottsdale, Arizona, United States

Site Status

St. Joseph's Hospital at Orange

Orange, California, United States

Site Status

Stanford Hospitals and Clinics

Stanford, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Community Health Network

Indianapolis, Indiana, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Capital Regional Medical Center

Jefferson City, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Baptist Cancer Center

Memphis, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Children's Hospital (Baylor College of Medicine)

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Countries

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United States

Other Identifiers

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PLX120-03

Identifier Type: -

Identifier Source: org_study_id

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