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Trial record 1 of 1 for:    AB-218 | glioma
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AB-218 Safety and Efficacy Study in Patients With IDH1 Mutant Glioma

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ClinicalTrials.gov Identifier: NCT05303519
Recruitment Status : Not yet recruiting
First Posted : March 31, 2022
Last Update Posted : April 6, 2022
Sponsor:
Information provided by (Responsible Party):
AnHeart Therapeutics Inc.

Brief Summary:

This is a Phase 2, multicenter, open label, two part, clinical study to evaluate the efficacy, safety, and PK of AB 218 in participants with recurrent or progressive histologically confirmed IDH1 mutant WHO Grade 2/3 glioma outside Japan. It was divided into 2 parts. Part 1 includes two stages: stage 1 and stage 2. Stage 1 further explores 5 dosing regimens in the glioma patients outside Japan. Stage 2 is dose expansion with one selected dosing regimen on non-surgical patients and surgical participants. The PK characteristics, safety and initial efficacy data will be assessed in Part 1. Part 2 is to evaluate the efficacy of AB-218 in the treatment of recurrent/progressive WHO CNS Grade 3 IDH1 mutant glioma.

Participants will receive oral AB-218 treatment continuously, with 28 days as a cycle, until disease progression, unacceptable toxicity, consent withdrawal, start of new anti-cancer therapy, investigator decision or death, upon whichever earlier.

Besides baseline, the anti-tumor response will be evaluated every 8 weeks following RANO or RANO-LGG criteria as applicable, until disease progression, consent withdrawal or death, upon whichever earlier.


Condition or disease Intervention/treatment Phase
Glioma Drug: AB-218 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-label, Two-parts Clinical Study to Evaluate the Efficacy and Safety of AB-218 in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Glioma
Estimated Study Start Date : January 2023
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : February 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AB-218 125mg bid
AB-218 125mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Drug: AB-218
AB-218 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Other Names:
  • DS-1001b
  • safusidenib

Experimental: AB-218 250mg bid
AB-218 250mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Drug: AB-218
AB-218 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Other Names:
  • DS-1001b
  • safusidenib

Experimental: AB-218 500mg qd
AB-218 500mg qd administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Drug: AB-218
AB-218 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Other Names:
  • DS-1001b
  • safusidenib

Experimental: AB-218 375mg bid
AB-218 375mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Drug: AB-218
AB-218 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Other Names:
  • DS-1001b
  • safusidenib

Experimental: AB-218 700mg bid
AB-218 700mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Drug: AB-218
AB-218 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AB-218 until disease progression or development of other unacceptable toxicity.
Other Names:
  • DS-1001b
  • safusidenib




Primary Outcome Measures :
  1. part1: Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From participants sign ICF to 30 days after last dose,average 2 years ]
    calculate Percentage and numbers of participants with adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 5.0

  2. part2: ORR by the IRC [ Time Frame: from drug treatment to 2 years ]
    ORR (defined as the proportion of participants with the best overall confirmed response of CR or PR[for RANO LGG] according to the appropriate tumor response criteria) as assessed by the IRC


Secondary Outcome Measures :
  1. Part 1 Stage 1: Cmax of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Peak Plasma Concentration (Cmax)

  2. Part 1 Stage 1: Tmax of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    the time for AB-218 to reach Cmax

  3. Part 1 Stage 1: AUC8h of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Area under the plasma concentration curve (AUC) from time 0 to 8 hours

  4. Part 1 Stage 1: AUC12h of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Area under the plasma concentration curve (AUC) from time 0 to 12 hours

  5. Part 1 Stage 1: AUC24h [QD only] of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Area under the plasma concentration curve (AUC) from time 0 to 24h hours for 500mg qd cohort

  6. Part 1 Stage 1: Ctrough of AB-218 [ Time Frame: on Days 2, 3, 4, 6, 8, 9 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 6 and 8 ]
    Lowest plasma concentration reached after AB-218 administration

  7. Part 1 Stage 2: Cmax of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Peak Plasma Concentration (Cmax)

  8. Part 1 Stage 2: Tmax of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    the time for AB-218 to reach Cmax

  9. Part 1 Stage 2: AUC6h of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Area under the plasma concentration curve (AUC) from time 0 to 6 hours

  10. Part 1 Stage 2: Ctrough of AB-218 [ Time Frame: on Days 4, 8 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 8 ]
    Lowest plasma concentration reached after AB-218 administration

  11. Part 1: ORR assessed by the investigator [ Time Frame: from drug treatment to 2 years ]
    ORR (defined as the proportion of participants with the best overall confirmed response of CR or PR [for RANO LGG] according to the appropriate tumor response criteria) as assessed by the Investigator

  12. Part 1: DOR assessed by the Investigator [ Time Frame: from drug treatment to 2 years ]
    Duration of response (DOR, defined as the time from the first date of objective response [CR or PR, to the first documented date of disease progression per RANO or RANO LGG or the date of death due to any cause, whichever occurs first) as assessed by the Investigator

  13. Part 1: DCR assessed by the Investigator [ Time Frame: from drug treatment to 2 years ]
    Disease control rate (DCR, defined as the proportion of patients with a best overall response of CR, PR, stable disease, or MR [for RANO LGG], per RANO or RANO LGG) as assessed by the Investigator

  14. Part 1: PFS assessed by the Investigator [ Time Frame: from drug treatment to 2 years ]
    Progression free survival (PFS, defined as the time from first dose of AB 218 until the date of disease progression per RANO or RANO LGG or death [by any cause in the absence of progression]) as assessed by the Investigator

  15. Part2: ORR, per RANO or RANO LGG, as applicable, by the Investigator [ Time Frame: from drug treatment to 2 years ]
    ORR (defined as the proportion of participants with the best overall confirmed response of CR or PR[for RANO LGG] according to the appropriate tumor response criteria) as assessed by the Investigator

  16. Part2: DOR assessed by the IRC and by the Investigator [ Time Frame: from drug treatment to 2 years ]
    DOR, defined as the time from the first date of objective response [CR or PR, to the first documented date of disease progression per RANO or RANO LGG or the date of death due to any cause, whichever occurs first) as assessed by the Investigator and IRC

  17. Part2: DCR assessed by the IRC and by the Investigator [ Time Frame: from drug treatment to 2 years ]
    DCR, defined as the proportion of patients with a best overall response of CR, PR, stable disease, or MR [for RANO LGG], per RANO or RANO LGG) as assessed by the Investigator and IRC

  18. Part2: PFS assessed by the IRC and by the Investigator [ Time Frame: from drug treatment to 2 years ]
    PFS, defined as the time from first dose of AB 218 until the date of disease progression per RANO or RANO LGG or death [by any cause in the absence of progression]) as assessed by the Investigator and IRC

  19. Part2: Overall survival (OS) [ Time Frame: from first dose of AB-218 to death ]
    OS: defined as the time from first dose of AB-218 until the date of death.

  20. Part2: Incidence of AEs and SAEs [ Time Frame: From participants sign ICF to 30 days after last dose, average 2 years ]
    Percentage and numbers of participants with adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 5.0

  21. Part2: Cmax of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Peak Plasma Concentration (Cmax)

  22. Part2: Tmax of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    the time for AB-218 to reach Cmax

  23. Part2: AUC6h of AB-218 [ Time Frame: on Cycle 1 Day 1 and Day 8 ]
    Area under the plasma concentration curve (AUC) from time 0 to 6 hours

  24. Part2: Ctrough of AB-218 [ Time Frame: on Days 4, 8 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 8 ]
    Lowest plasma concentration reached after AB-218 administration


Other Outcome Measures:
  1. for part 1 stage 2 surgical participants: AB-218 concentrations in both plasma and tumor tissues [ Time Frame: in the 5th week after first AB-218 dose ]
    The concentration of AB-218 in tumor tissue samples collected at the time of tumor resection and plasma samples.

  2. for part 1 stage 2 surgical participants: 2-hydroxyglutarate (2-HG) concentrations in the tumor tissue [ Time Frame: at the time of pre-treatment, and in the 5th week after first AB-218 dose ]
    The concentration of 2-HG in tumor tissue samples at the time of tumor resection posttreatment and in tumor tissue samples submitted pretreatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Age:

  1. Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).

    Type of Patient and Disease Characteristics:

  2. In Part 1, patient must have histologically confirmed IDH1 mutated WHO Grade 2 glioma or Grade 3 glioma.
  3. Patient participating in the Part 1 Stage 2 Surgery Cohort is expected to have a stable disease at least and eligible for surgery after one-cycle treatment of AB-218, as deemed by Investigator.
  4. In Part 2, patient must have histologically confirmed IDH mutated WHO Grade 3 glioma.
  5. Patient has available archived primary tumor biopsy or surgical specimens, or biopsies of recurrence of metastasis for retrospective IDH mutation confirmation, other glioma mutation testing to support the reconfirmation of Glioma WHO classification and explorative studies. At least 100-micron length of formalin fixed paraffin embedded (FFPE) tissue or tissue block shall be available for enrollment and shipped to the designated laboratory. If unavailable, patient could still be eligible after the assessment by the Sponsor upon the sufficiency of assessment.
  6. The IDH mutation, 1p/19q co-deletion and CDKN2A/B homozygous deletion are determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Prior clinical pathology report fulfilling the diagnosis criteria prior to screening with tumor samples collected is acceptable for subject enrollment in both Part 1 and Part 2. If no such report is available, samples shall be sent for the designated central lab for the determination retrospectively of related gene abnormalities.
  7. Patient must have no more than 2 disease recurrence or progression and have failed to the standard therapy that patient has not responded to this therapy.
  8. Patient did not receive the prior therapy targeted to IDH1 mutation
  9. Patient must have a measurable lesion(s) as per the RANO or RANO-LGG criteria, as applicable. The lesion (s) must be visible on two or more axial slices and have perpendicular diameters of at least 10 × 10 mm.
  10. Patient must have life expectancy ≥ 3 months.
  11. Patient must have Karnofsky Performance Status (KPS) score ≥ 60.
  12. Patient must have mild or moderate neurologic symptoms in accordance with the Neurological Assessment in Neuro-Oncology Scale (NANO).
  13. Patient who has adequate organ functions as defined below:

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2.5 × upper limit of normal (ULN)
    • Total bilirubin: ≤ 1.5 × ULN
    • Absolute neutrophil count: ≥ 1,500/μL
    • Platelet count: ≥ 100,000/μL (or ≥ 50,000/μL for prior temozolomide therapy)
    • Hemoglobin: ≥ 9.0 g/dL
    • Creatinine clearance (Cockcroft Gault Formula) ≥ 60 mL/min An out of range laboratory test will be repeated up to 2 times before declaring a screen failure, and after expiration of screening window, patients will be re screened.
  14. Recovery to Grade 1 or baseline from any toxicities due to prior therapies (except conditions such as alopecia and irreversible changes associated with radiation therapy).

    Sex and Contraceptive/Barrier Requirements:

  15. Female patients who engage in heterosexual intercourse must be of non childbearing potential, defined as either surgically sterile (e.g., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), OR be postmenopausal with at least 1 year of amenorrhea, OR must agree to use a highly effective method of contraception from the beginning of Screening until at least 90 days after the last dose of study drug.

    Acceptable highly effective methods of contraception include:

    • Combined estrogen progestin oral hormonal contraception associated with consistent inhibition of ovulation.
    • Desogestrel based progestin only contraception associated with consistent inhibition of ovulation; this includes oral, injectable, and implantable methods
    • Intravaginal and transdermal hormone delivery methods
    • Intrauterine device (with or without hormone elution)
    • Bilateral tubal occlusion or ligation (must be documented)
    • Vasectomized partner (must be documented) or Sexual abstinence (only when it is the usual and preferred lifestyle of the patient).
  16. Male patients should agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 90 days after the last dose of study drug (or be surgically sterile [e.g., vasectomy with documentation]; or remain abstinent [when this is in line with the preferred and usual lifestyle]). Male patients should also agree to not donate sperm for the duration of the study and until at least 90 days after the last dose of study drug.

    Informed Consent:

  17. Patient should be willing to provide written ICF.
  18. Ability to undergo the protocol specified procedures, including blood tests and urinalysis.

Exclusion Criteria:

Medical Conditions:

  1. Patients with history or complication of any of the following diseases within 3 months prior to the initial dose of the study drug:

    • Myocardial infarction
    • Severe or unstable angina pectoris
    • Coronary or peripheral endovascular treatment
    • Heart failure
    • Cerebrovascular disorder including transient ischemic attack, stroke, central nervous system (CNS) bleeding.
  2. Uncontrolled active systemic fungal, bacterial, or other infection (despite appropriate antibiotics or other treatment).
  3. Gastrointestinal diseases that may interfere with oral ingestion of the study drug or may affect absorption of the study drug.
  4. Psychiatric disease or symptoms that may interfere with the patient's continuous participation in the study.
  5. Patients should be tested for SARS-CoV-2 and those with active infection detected using either molecular or antigen tests in accordance with local testing guidelines will be excluded.

    Prior/Concomitant Therapy:

  6. Prior anti cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:

    • Systemic drug therapies: within 3 weeks
    • Surgery: within 3 weeks
    • Radiation therapy: within 12 weeks
    • Investigational agents: within 5 half-lives for other investigational agents
  7. Patients taking substrates of cytochrome CYP2C8, CYP2C9, and CYP3A4 with narrow therapeutic window, should be excluded unless they can be transferred to other medications prior to enrolling. Patients taking sensitive CYP 2C8, 2C9 or 3A4 substrate medications may require dosage adjustment unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.

    Diagnostic Assessments:

  8. Advanced arrhythmia of Grade ≥ 2 per NCI CTCAE v5.0, uncontrolled atrial fibrillation (any grade) and corrected QT interval by Fredericia's formula (QTcF) > 470 msec.
  9. Evidence of intraspinal dissemination by magnetic resonance imaging (MRI).
  10. Positive test results for human immunodeficiency virus (HIV) antibody.
  11. Positive test results for hepatitis B surface (HBs) antigen and/or hepatitis C virus (HCV) antibody. Patients who have tested positive for hepatitis B core (HBc) antibody and/or HBs antibody, despite negative test results for HBs antigen, may be enrolled only if they have negative finding on quantitative hepatitis B virus (HBV)-DNA assays with anti-HBV treatment is allowing during study period. Patients who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before enrolment; those who are hepatitis C PCR positive will be excluded.

    Other Exclusions:

  12. Pregnant or breastfeeding female patient.
  13. Known hypersensitivity to the study drug or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of the study drug.

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): NCT05303519


Contacts
Layout table for location contacts
Contact: Yan Li +1 212 466 6378 yli@anhearttherapeutics.com
Contact: Weiqing Wang +1 212 466 6378 wqwang@anhearttherapeutics.com

Sponsors and Collaborators
AnHeart Therapeutics Inc.
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Responsible Party: AnHeart Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT05303519    
Other Study ID Numbers: AB-218-G203
First Posted: March 31, 2022    Key Record Dates
Last Update Posted: April 6, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue