Advanced Unresectable Solid TumorsPhase 1/2NCT02428712
A Study of FORE8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors
A Phase 1/2 study testing FORE8394 in people with Advanced Unresectable Solid Tumors and BRAF-mutated Tumors, run by Fore Biotherapeutics at 13 sites in United States.
Trial summary
The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of FORE8394. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Advanced Unresectable Solid Tumors, BRAF-mutated Tumors
- What is being tested?
- FORE8394
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 13 sitesUnited States
- Study dates
- Apr 2015to 12 Jul 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 19Show fewer
- 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.
- 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.
Who cannot join
- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Karmanos Cancer Institute
Detroit, Michigan, 48201
MD Anderson Cancer Center
Houston, Texas, 77030
Texas Children's Hospital (Baylor College of Medicine)
Houston, Texas, 77030
Community Health Network
Indianapolis, Indiana, 46011
Capital Regional Medical Center
Jefferson City, Missouri, 65101
Baptist Cancer Center
Memphis, Tennessee, 38120
University of Miami
Miami, Florida, 33136
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
St. Joseph's Hospital at Orange
Orange, California, 92868
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
HonorHealth
Scottsdale, Arizona, 85258
Stanford Hospitals and Clinics
Stanford, California, 94305
About this study
Official title: A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of FORE8394 in Patients With Advanced Unresectable Solid Tumors
The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of FORE8394.
Read the detailed description
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.
- Being tested
- FORE8394
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FORE8394Drug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: FORE8394 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve (AUC) of FORE8394
Measured: First dose of FORE8394 up to 30 days after end of treatment
Maximum concentration (Cmax) of FORE8394
Measured: First dose of FORE8394 up to 30 days after end of treatment
Time to peak concentration (Tmax) of FORE8394
Measured: First dose of FORE8394 up to 30 days after end of treatment
Half life (T1/2) of FORE8394
Measured: 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.
Measured: 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.
Measured: 2 years
Compare AUC of FORE8394 with FORE8394
Measured: First dose of FORE8394 up to 30 days after end of treatment
Compare Cmax of FORE8394 with FORE8394
Measured: First dose of FORE8394 up to 30 days after end of treatment
Compare Tmax of FORE8394 with FORE8394
Measured: First dose of FORE8394 up to 30 days after end of treatment
Compare T1/2 of FORE8394 with FORE8394
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 5 years
Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study startApr 2015
- Primary completion12 Jul 2024
- Study completion12 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Unresectable Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fore Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stacie Peacock Shepherd, MD, PhD, Study chair, Fore Biotherapeutics U.S. Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02428712
- Sponsor's protocol ID
- PLX120-03
- Status last verified
- Jul 2025
- First submitted
- 20 Apr 2015
- Last updated
- 29 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of FORE8394 in Patients With Advanced Unresectable Solid Tumors
- ClinicalTrials.gov ID
- NCT02428712
- Acronym / sponsor ID
- PLX120-03
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Fore BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Apr 2015 (actual)
- Primary completion
- 12 Jul 2024 (actual)
- Study completion
- 12 Jul 2024 (actual)
- First posted
- 29 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of FORE8394.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FORE8394 | Experimental | Drug: FORE8394Group 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 |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- 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 - RP2D Redefinition Extension: Following RP2D redefinition, extension participants must meet criteria for Cohort 3 or Cohort 4 as specified below:
- Measurable disease by RECIST 1.1.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FORE8394 | Drug | FORE8394 |
Primary outcome
Area under the curve (AUC) of FORE8394
Time frame: First dose of FORE8394 up to 30 days after end of treatment
Maximum concentration (Cmax) of FORE8394
Time frame: First dose of FORE8394 up to 30 days after end of treatment
Time to peak concentration (Tmax) of FORE8394
Time frame: First dose of FORE8394 up to 30 days after end of treatment
Half life (T1/2) of FORE8394
Time frame: 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.
Time frame: 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.
Time frame: 2 years
Compare AUC of FORE8394 with FORE8394
Time frame: First dose of FORE8394 up to 30 days after end of treatment
Compare Cmax of FORE8394 with FORE8394
Time frame: First dose of FORE8394 up to 30 days after end of treatment
Compare Tmax of FORE8394 with FORE8394
Time frame: First dose of FORE8394 up to 30 days after end of treatment
Compare T1/2 of FORE8394 with FORE8394
Time frame: 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.
Time frame: 5 years
3 secondary outcomes
To evaluate the duration of response (defined as time of initial response to progressive disease or death) at the applicable RP2D in Dose Extension.
Time frame: 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.
Time frame: 5 years
Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
Related trials for Advanced Unresectable Solid Tumors
RecruitingPhase 2
A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Solid Tumors, HER2 Mutation
Active, not recruitingPhase 3
Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)
PD-L1-positive, Locally Advanced (Unresectable Stage IIIB/C) or Metastatic NSCLC
RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Active, not recruitingPhase 2
Testing Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
RecruitingPhase 1
Study of RGT-490 in Patients With PIK3CA-Mutated Advanced Solid Tumors
Breast Cancer, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stacie Peacock Shepherd, MD, PhD study chair
Fore Biotherapeutics U.S. Inc.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FORE8394 in people with Advanced Unresectable Solid Tumors and BRAF-mutated Tumors, run by Fore Biotherapeutics at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the curve (AUC) of FORE8394 (time frame: First dose of FORE8394 up to 30 days after end of treatment). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.