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

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ClinicalTrials.gov Identifier: NCT02428712
Recruitment Status : Recruiting
First Posted : April 29, 2015
Last Update Posted : July 19, 2022
Sponsor:
Information provided by (Responsible Party):
Fore Biotherapeutics

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

Condition or disease Intervention/treatment Phase
Advanced Unresectable Solid Tumors BRAF-mutated Tumors Drug: FORE8394 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of FORE8394 in Patients With Advanced Unresectable Solid Tumors
Study Start Date : April 2015
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023

Arm Intervention/treatment
Experimental: 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
Drug: FORE8394



Primary Outcome Measures :
  1. Area under the curve (AUC) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  2. Maximum concentration (Cmax) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  3. Time to peak concentration (Tmax) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  4. Half life (T1/2) of FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  5. 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 ]
  6. 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 ]
  7. Compare AUC of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  8. Compare Cmax of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  9. Compare Tmax of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  10. Compare T1/2 of FORE8394 with FORE8394 [ Time Frame: First dose of FORE8394 up to 30 days after end of treatment ]
  11. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02428712


Contacts
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Contact: Jessica Rine 610-442-4517 jessica.rine@fore.bio

Locations
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Sponsors and Collaborators
Fore Biotherapeutics
Investigators
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Study Chair: Stacie Peacock Shepherd, MD, PhD Fore Biotherapeutics U.S. Inc.
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Responsible Party: Fore Biotherapeutics
ClinicalTrials.gov Identifier: NCT02428712    
Other Study ID Numbers: PLX120-03
First Posted: April 29, 2015    Key Record Dates
Last Update Posted: July 19, 2022
Last Verified: July 2022
Additional relevant MeSH terms:
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Neoplasms