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

NCT02428712 | Completed Phase 1

• 1 other identifier: PLX120-03
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 13

Brief Summary

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

Conditions

Advanced Unresectable Solid Tumors; BRAF-mutated Tumors

Outcome Measures

Primary Outcomes (11)

• Area under the curve (AUC) of FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• Maximum concentration (Cmax) of FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• Time to peak concentration (Tmax) of FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• Half life (T1/2) of FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• Number of participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v4.0.

  First dose of FORE8394 up to 30 days after end of treatment

• To identify the recommended Phase 2 dose (RP2D) of FORE8394 in Group A (adult patients) for further evaluation in Dose Extension.

  2 years

• Compare AUC of FORE8394 with FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• Compare Cmax of FORE8394 with FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• Compare Tmax of FORE8394 with FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• Compare T1/2 of FORE8394 with FORE8394

  First dose of FORE8394 up to 30 days after end of treatment

• To determine the overall response rate of FORE8394 treatment at the applicable RP2D in a) Group A, Cohort 1, and b) Group A, Cohort 2.

  5 years

Secondary Outcomes (3)

• To evaluate the duration of response (defined as time of initial response to progressive disease or death) at the applicable RP2D in Dose Extension.

  5 years

• To evaluate the progression free survival (defined as time of first dose to progressive disease or death) at the applicable RP2D in Dose Extension.

  5 years

• Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study

  5 years

Study Arms (1)

FORE8394

EXPERIMENTAL

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

Drug: FORE8394

Interventions

FORE8394 DRUG

FORE8394

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients with solid tumors (as of Amendment 10, only subjects with glioma tumors) driven by an activating BRAF-V600 mutation
• Patients with no prior exposure to BRAF-directed therapy and for whom no standard therapy exists.
• Phase 2a-Dose Extension-Cohort 2
• Patients with solid tumors driven by an activating BRAF non-V600 mutation, which can include a point mutation, gene amplification, fusion, insertion, or deletion
• 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:
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fore Biotherapeutics: lead

Study Sites (13)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

St. Joseph's Hospital at Orange

Orange, California, 92868, United States

Location

Stanford Hospitals and Clinics

Stanford, California, 94305, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Community Health Network

Indianapolis, Indiana, 46011, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Capital Regional Medical Center

Jefferson City, Missouri, 65101, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Hospital (Baylor College of Medicine)

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Study Officials

• Stacie Peacock Shepherd, MD, PhD

  Fore Biotherapeutics U.S. Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2015
• First Posted: April 29, 2015
• Study Start: April 1, 2015
• Primary Completion: July 12, 2024
• Study Completion: July 12, 2024
• Last Updated: July 29, 2025

Record last verified: 2025-07

Locations

US (13)