Safusidenib Phase 2 Study in IDH1 Mutant Glioma

NCT ID: NCT05303519

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-05

Study Completion Date

2028-03-01

Brief Summary

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This is a 2-part study. The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants with recurrent/progressive IDH1-mutant World Health Organization (WHO) Grade 2 or Grade 3 glioma.

The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 3 astrocytoma with high-risk features or Grade 4 IDH1-mutant astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double blind, and placebo controlled.

Detailed Description

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Part 1 of this study will enroll up to 25 patients that 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.was fully enrolled as of 19 Dec 2023 and participants are currently ongoing.

Part 2 will include approximately 100 participants with IDH1-mutant astrocytoma, Grade 3 with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Participants will be randomized (1:1) after their last dose of adjuvant temozolomide to receive either oral safusidenib 250 mg BID or placebo in 28-day continuous cycles. Patients will continue treatment until progression of disease or until other discontinuation criteria are met. The tumor response evaluation will be conducted on a regular basis until progression of disease per Blinded Independent Central Review (BICR), consent withdrawal, or death, whichever occurs first. Long-term survival follow-up will be conducted as well.

Conditions

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Glioma Astrocytoma, Grade IV IDH1-mutant Glioma Astrocytoma, IDH-Mutant, Grade 3 Astrocytoma, IDH-Mutant, Grade 4

Keywords

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safusidenib IDH1-mutant glioma astrocytoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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safusidenib 125mg bid (part 1)

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.

Group Type EXPERIMENTAL

safusidenib

Intervention Type DRUG

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.

safusidenib 250mg bid (part 1)

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.

Group Type EXPERIMENTAL

safusidenib

Intervention Type DRUG

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.

safusidenib 500mg qd (part 1)

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.

Group Type EXPERIMENTAL

safusidenib

Intervention Type DRUG

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.

safusidenib 375mg bid (part 1)

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.

Group Type EXPERIMENTAL

safusidenib

Intervention Type DRUG

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.

safusidenib 500mg bid (part 1)

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.

Group Type EXPERIMENTAL

safusidenib

Intervention Type DRUG

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.

safusidenib 250mg bid (Part 2)

safusidenib administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment until disease progression or another reason for discontinuation occurs.

Group Type EXPERIMENTAL

safusidenib

Intervention Type DRUG

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.

placebo (Part 2)

Placebo administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with placebo until disease progression or another reason for discontinuation occurs.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with placebo until disease progression or another reason for discontinuation occurs.

Interventions

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safusidenib

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.

Intervention Type DRUG

Placebo

Placebo administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with placebo until disease progression or another reason for discontinuation occurs.

Intervention Type DRUG

Other Intervention Names

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DS-1001b AB-218

Eligibility Criteria

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Inclusion Criteria

1. Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. 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.

4\. 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.

5\. Patient has received no more than 2 prior therapies for disease recurrence/progression.

6\. Patient has disease recurrence or progression or cannot tolerate the most recent therapy.

7\. 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.


1. Must be ≥18 years old at the time of signing the ICF.
2. Diagnosis of histologically confirmed IDH1-mutant Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.
3. Have an IDH1 mutation (R132H/C/G/S/L) based on IHC (R132H only), polymerase chain reaction (PCR), or next-generation sequencing (NGS). CDKN2A/B status and at least 1 of the following must be confirmed: absence of 1p19q co-deletion by fluorescence in situ hybridization, array comparative genomic hybridization, or NGS; presence of an ATRX loss of function mutation by NGS; or loss of normal ATRX expression by IHC. A validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory must be used for all of the aforementioned results. Documentation of biomarker status, including redacted molecular pathology and NGS reports, must be provided during Screening.
4. Must not have experienced disease recurrence or disease progression.
5. Participants must have completed radiation therapy with a minimum of 90% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant temozolomide and have no evidence of disease progression. Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide.
6. Must agree to submit sufficient tumor tissue for retrospective biomarker and histological analyses. This requirement may be waived in rare circumstances with approval by the Sponsor.
7. Has adequate hematologic and organ functions

Exclusion Criteria

* 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..
* Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.


1. Participants may not have received any anticancer treatments other than surgery, radiation, concurrent/adjuvant temozolomide, and tumor-treating fields. Tumor-treating fields must be discontinued prior to randomization.
2. Participants with prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.
3. Have brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension.
4. Significant functional or neurocognitive deficits, including uncontrolled seizures, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
5. Evidence of diffuse leptomeningeal disease by MRI.
6. History of significant cardiac disease within 12 months prior to randomization.
7. If taking corticosteroids, must be on a stable or decreasing dose for the 14 days prior to randomization.
8. Participants with other malignancies must have received curative treatment and been disease-free for at least 3 years. Curatively resected non-melanoma skin cancer or curatively treated carcinoma in situ is allowed.
9. Have a condition that would interfere with, or increase the risk of, study participation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AnHeart Therapeutics Inc.

INDUSTRY

Sponsor Role collaborator

Nuvation Bio Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status RECRUITING

Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status RECRUITING

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status RECRUITING

University of California, Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status RECRUITING

Stanford University

Palo Alto, California, United States

Site Status NOT_YET_RECRUITING

University of California

San Francisco, California, United States

Site Status NOT_YET_RECRUITING

University of Colorado Health Cancer Care

Aurora, Colorado, United States

Site Status NOT_YET_RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

University of Florida Health

Gainesville, Florida, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic - Florida

Jacksonville, Florida, United States

Site Status RECRUITING

University of Miami Health

Miami, Florida, United States

Site Status NOT_YET_RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status NOT_YET_RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Henry Ford Hospital

Detroit, Michigan, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status NOT_YET_RECRUITING

Rutgers Cancer Institute

New Brunswick, New Jersey, United States

Site Status RECRUITING

New York University Langone Health

New York, New York, United States

Site Status NOT_YET_RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Duke Cancer Institute

Durham, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status NOT_YET_RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

Huntsman Cancer Insititute, University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

UVA Health, Emily Couric Clinical Cancer Cente

Charlottesville, Virginia, United States

Site Status RECRUITING

Fred Hutch Cancer Center

Seattle, Washington, United States

Site Status NOT_YET_RECRUITING

University of Wisconsin Health

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Trials at Nuvation Bio

Role: CONTACT

Phone: 332-208-6102

Email: [email protected]

Facility Contacts

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Shirley Gibbs

Role: primary

Brittany Mason

Role: primary

Ciara Lugo

Role: primary

Soheila Abbassi

Role: primary

Role: backup

Jason Ledesma

Role: primary

Sahara Rout

Role: primary

Karishma Kumar-Wessel

Role: primary

Stephanie Biller

Role: primary

Amy Rodrigues

Role: primary

Alicia Wyrick

Role: primary

Mayo Clinic Mailbox

Role: primary

Irene Marino

Role: primary

Kelvisha Norton

Role: primary

Xuam Lam

Role: primary

Julie Miller

Role: primary

Amanda Dresser

Role: primary

Phillip Alther

Role: primary

Sonia Velazquez

Role: primary

Leslie Nehring

Role: primary

Kassie DiOrio

Role: primary

Olga Garduno-Ortega

Role: primary

Research Nurse Navigator

Role: primary

Nancy Keith

Role: primary

Madeleine Ruff

Role: backup

Jessicka Hamilton

Role: primary

Marci Ciolfi

Role: primary

Omar Raslan

Role: primary

Eva Gachimova

Role: primary

Rachel Kingsford

Role: primary

CJ Woodburn, 434-243-9900

Role: primary

Madhuri Poduri

Role: primary

Erin Clements

Role: primary

Other Identifiers

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AB-218-G203

Identifier Type: -

Identifier Source: org_study_id