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

Advanced Unresectable Solid Tumors Clinical Trial

Official title:

A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of FORE8394 in Patients With Advanced Unresectable Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02428712
• Other study ID #: PLX120-03
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2015
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Fore Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 113
• Est. completion date: December 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

Inclusion Criteria- Group A:

• 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- Group A:

• 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.

Related Conditions & MeSH terms

• Advanced Unresectable Solid Tumors
• BRAF-mutated Tumors
• Neoplasms

Intervention

Drug:
• FORE8394

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	Texas Children's Hospital (Baylor College of Medicine)	Houston	Texas
United States	Community Health Network	Indianapolis	Indiana
United States	Capital Regional Medical Center	Jefferson City	Missouri
United States	Baptist Cancer Center	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	St. Joseph's Hospital at Orange	Orange	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	HonorHealth	Scottsdale	Arizona
United States	Stanford Hospitals and Clinics	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Fore Biotherapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve (AUC) of FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	Maximum concentration (Cmax) of FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	Time to peak concentration (Tmax) of FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	Half life (T1/2) of FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	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
Primary	To identify the recommended Phase 2 dose (RP2D) of FORE8394 in Group A (adult patients) for further evaluation in Dose Extension.		2 years
Primary	Compare AUC of FORE8394 with FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	Compare Cmax of FORE8394 with FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	Compare Tmax of FORE8394 with FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	Compare T1/2 of FORE8394 with FORE8394		First dose of FORE8394 up to 30 days after end of treatment
Primary	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	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
Secondary	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
Secondary	Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study		5 years