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Safusidenib Phase 2 Study in IDH1 Mutant Glioma

Primary Purpose

Glioma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
safusidenib
Sponsored by
AnHeart Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Columbia University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

safusidenib 125mg bid

safusidenib 250mg bid

safusidenib 500mg qd

safusidenib 375mg bid

safusidenib 500mg bid

Arm Description

safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.

safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.

safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.

safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.

safusidenib 500mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.

Outcomes

Primary Outcome Measures

part1: Incidence of adverse events (AEs) and serious adverse events (SAEs)
calculate Percentage and numbers of participants with adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 5.0
part2: ORR by the IRC
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

Part 1 Stage 1: Cmax of safusidenib
Peak Plasma Concentration (Cmax)
Part 1 Stage 1: Tmax of safusidenib
the time for safusidenib to reach Cmax
Part 1 Stage 1: AUC8h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 8 hours
Part 1 Stage 1: AUC12h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 12 hours
Part 1 Stage 1: AUC24h [QD only] of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 24h hours for 500mg qd cohort
Part 1 Stage 1: Ctrough of safusidenib
Lowest plasma concentration reached after AB-218 administration
Part 1 Stage 2: Cmax of safusidenib
Peak Plasma Concentration (Cmax)
Part 1 Stage 2: Tmax of safusidenib
the time for AB-218 to reach Cmax
Part 1 Stage 2: AUC6h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 6 hours
Part 1 Stage 2: Ctrough of safusidenib
Lowest plasma concentration reached after AB-218 administration
Part 1: ORR assessed by the investigator
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
Part 1: DOR assessed by the Investigator
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
Part 1: DCR assessed by the Investigator
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
Part 1: PFS assessed by the Investigator
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
Part2: ORR, per RANO or RANO LGG, as applicable, by the Investigator
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
Part2: DOR assessed by the IRC and by the Investigator
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
Part2: DCR assessed by the IRC and by the Investigator
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
Part2: PFS assessed by the IRC and by the Investigator
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
Part2: Overall survival (OS)
OS: defined as the time from first dose of safusidenib until the date of death.
Part2: Incidence of AEs and SAEs
Percentage and numbers of participants with adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 5.0
Part2: Cmax of safusidenib
Peak Plasma Concentration (Cmax)
Part2: Tmax of safusidenib
the time for safusidenib to reach Cmax
Part2: AUC6h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 6 hours
Part2: Ctrough of safusidenib
Lowest plasma concentration reached after safusidenib administration

Full Information

First Posted
March 13, 2022
Last Updated
May 23, 2023
Sponsor
AnHeart Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05303519
Brief Title
Safusidenib Phase 2 Study in IDH1 Mutant Glioma
Official Title
A Phase 2, Multicenter, Open Label, Two Parts Clinical Study to Evaluate the Efficacy and Safety of Safusidenib Erbumine in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 26, 2023 (Anticipated)
Primary Completion Date
March 31, 2027 (Anticipated)
Study Completion Date
July 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AnHeart Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 2, multicenter, open label, two parts, clinical study to evaluate the efficacy, safety, and PK of safusidenib. Patients with recurrent or progressive histologically confirmed IDH1 mutant WHO Grade 2/3 glioma10 outside Japan, will be enrolled in this study. It was divided into 2 parts. Part 1: Up to 25 patients will be randomized 1:1:1:1:1 (5 patients per group) to receive one of the daily oral doses of safusidenib at 125 mg twice a day (BID), 250 mg BID, 500 mg once daily (QD), 375 mg BID, or 500 mg BID. The PK characteristics and safety and initial efficacy data will be assessed in Part 1. Part 2: It is planned to open 2 glioma subtype cohorts: Grade 2 and Grade 3 glioma cohorts with 30 eligible patients enrolled in each cohort. Total 60 patients will be enrolled. Part 2 is to evaluate the efficacy of safusidenib in the treatment of recurrent/progressive WHO CNS Grade 2 and grade 3 IDH1 mutant glioma. Exploratory Surgery Cohort: This cohort will be conducted in parallel with Part 2, for explorative purpose once RP2D is decided. 5 patients with primarily enhancing lesions and other 5 with primarily non-enhancing lesions will be enrolled. Participants will receive oral safusidenib 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
95 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
safusidenib 125mg bid
Arm Type
Experimental
Arm Description
safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.
Arm Title
safusidenib 250mg bid
Arm Type
Experimental
Arm Description
safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.
Arm Title
safusidenib 500mg qd
Arm Type
Experimental
Arm Description
safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.
Arm Title
safusidenib 375mg bid
Arm Type
Experimental
Arm Description
safusidenib 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 safusidenib until disease progression or development of other unacceptable toxicity.
Arm Title
safusidenib 500mg bid
Arm Type
Experimental
Arm Description
safusidenib 500mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
safusidenib
Other Intervention Name(s)
DS-1001b, AB-218
Intervention Description
safusidenib administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with agent safusidenib until disease progression or development of other unacceptable toxicity.
Primary Outcome Measure Information:
Title
part1: Incidence of adverse events (AEs) and serious adverse events (SAEs)
Description
calculate Percentage and numbers of participants with adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 5.0
Time Frame
From participants sign ICF to 30 days after last dose,average 2 years
Title
part2: ORR by the IRC
Description
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
Time Frame
from drug treatment to 2 years
Secondary Outcome Measure Information:
Title
Part 1 Stage 1: Cmax of safusidenib
Description
Peak Plasma Concentration (Cmax)
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 1: Tmax of safusidenib
Description
the time for safusidenib to reach Cmax
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 1: AUC8h of safusidenib
Description
Area under the plasma concentration curve (AUC) from time 0 to 8 hours
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 1: AUC12h of safusidenib
Description
Area under the plasma concentration curve (AUC) from time 0 to 12 hours
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 1: AUC24h [QD only] of safusidenib
Description
Area under the plasma concentration curve (AUC) from time 0 to 24h hours for 500mg qd cohort
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 1: Ctrough of safusidenib
Description
Lowest plasma concentration reached after AB-218 administration
Time Frame
on Days 2, 3, 4, 6, 8, 9 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 6 and 8
Title
Part 1 Stage 2: Cmax of safusidenib
Description
Peak Plasma Concentration (Cmax)
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 2: Tmax of safusidenib
Description
the time for AB-218 to reach Cmax
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 2: AUC6h of safusidenib
Description
Area under the plasma concentration curve (AUC) from time 0 to 6 hours
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part 1 Stage 2: Ctrough of safusidenib
Description
Lowest plasma concentration reached after AB-218 administration
Time Frame
on Days 4, 8 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 8
Title
Part 1: ORR assessed by the investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part 1: DOR assessed by the Investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part 1: DCR assessed by the Investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part 1: PFS assessed by the Investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part2: ORR, per RANO or RANO LGG, as applicable, by the Investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part2: DOR assessed by the IRC and by the Investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part2: DCR assessed by the IRC and by the Investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part2: PFS assessed by the IRC and by the Investigator
Description
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
Time Frame
from drug treatment to 2 years
Title
Part2: Overall survival (OS)
Description
OS: defined as the time from first dose of safusidenib until the date of death.
Time Frame
from first dose of safusidenib to death
Title
Part2: Incidence of AEs and SAEs
Description
Percentage and numbers of participants with adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 5.0
Time Frame
From participants sign ICF to 30 days after last dose, average 2 years
Title
Part2: Cmax of safusidenib
Description
Peak Plasma Concentration (Cmax)
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part2: Tmax of safusidenib
Description
the time for safusidenib to reach Cmax
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part2: AUC6h of safusidenib
Description
Area under the plasma concentration curve (AUC) from time 0 to 6 hours
Time Frame
on Cycle 1 Day 1 and Day 8
Title
Part2: Ctrough of safusidenib
Description
Lowest plasma concentration reached after safusidenib administration
Time Frame
on Days 4, 8 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 8
Other Pre-specified Outcome Measures:
Title
for part 1 stage 2 surgical participants: Safusidenib concentrations in both plasma and tumor tissues
Description
The concentration of safusidenib in tumor tissue samples collected at the time of tumor resection and plasma samples.
Time Frame
in the 5th week after first safusidenib dose
Title
for part 1 stage 2 surgical participants: 2-hydroxyglutarate (2-HG) concentrations in the tumor tissue
Description
The concentration of 2-HG in tumor tissue samples at the time of tumor resection posttreatment and in tumor tissue samples submitted pretreatment.
Time Frame
at the time of pre-treatment, and in the 5th week after first safusidenib dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF). Type of Patient and Disease Characteristics Patient must have histologically confirmed recurrent or progressive WHO Grade 2 glioma or Grade 3 glioma with IDH1 R132H or R132C mutation confirmed by immunohistochemistry or molecular genetic testing. Patient has available archived primary tumor biopsy or surgical specimens, or biopsies of recurrence of metastasis for retrospective IDH mutation confirmation and other genes testing to support the reconfirmation of Glioma WHO classification and explorative studies. The IDH mutation, and other applicable gene/molecular alterations (see Table 10-2) 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 patient enrollment in both Part 1 and Part 2. Patient has received no more than 2 prior therapies for disease recurrence/progression. Patient has disease recurrence or progression or cannot tolerate the most recent therapy. Patient must have a measurable lesion(s) as per the RANO-HGG criteria for primarily enhancing lesions or RANO-LGG criteria for primarily non-enhancing lesions. The lesion (s) must be visible on 2 or more axial slices and have perpendicular diameters of at least 10 × 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1. Patient must have life expectancy ≥ 3 months. Patient must have KPS score ≥ 60. Patient who has adequate organ functions as defined below: AST and 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. Recovery to Grade 1 or baseline from any toxicities due to prior therapies (except conditions such as alopecia, temozolomide-induced lymphopenia and irreversible changes associated with radiation therapy). 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 safusidenib. 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) Additional information for contraceptive measurements is provided in Appendix 4: Contraceptive and Barrier Guidance. 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 safusidenib (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 safusidenib. Patient should be willing to provide written ICF. Ability to undergo the protocol-specified procedures, including blood tests and urinalysis. Exclusion Criteria: Patients with history or complication of any of the following diseases within 6 months prior to the initial dose of safusidenib: 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. Uncontrolled active systemic fungal, bacterial, or other infection (despite appropriate antibiotics or other treatment). Gastrointestinal diseases that may interfere with oral ingestion of safusidenib or may affect absorption of safusidenib. Psychiatric disease or symptoms that may interfere with the patient's continuous participation in the study. Patients should be tested for severe acute respiratory syndrome coronavirus 2 (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 anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment: Systemic drug therapies: within 3 weeks (lomustine within 6 weeks) Surgery: within 3 weeks Radiation therapy: within 12 weeks Investigational agents: within 5 half-lives for other investigational agents Patient did receive the prior therapy targeted to IDH1 mutation. Patients taking substrates of cytochrome CYP2C8, CYP2C9, and CYP3A4 (See Appendix 7) 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. Patients taking sensitive substrates of P-gp and BCRP transporters (See Appendix 7) should be excluded unless they can be transferred to other medications prior to enrolling. Patients taking sensitive substrates of P-gp and BCRP may require dosage adjustment unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing. 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. Evidence of intraspinal dissemination or diffuse leptomeningeal disease by MRI. Positive test results for human immunodeficiency virus (HIV) antibody. 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 and the 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 enrollment; those who are hepatitis C PCR positive will be excluded. Pregnant or breastfeeding female patient. Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Li
Phone
+1 212 466 6378
Email
yli@anhearttherapeutics.com
First Name & Middle Initial & Last Name or Official Title & Degree
Weiqing Wang
Phone
+1 212 466 6378
Email
wqwang@anhearttherapeutics.com
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ariana Vasquez
First Name & Middle Initial & Last Name & Degree
Fabio Iwamoto, MD

12. IPD Sharing Statement

Learn more about this trial

Safusidenib Phase 2 Study in IDH1 Mutant Glioma

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