SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance) (SIGMA)

March 3, 2026 updated by: Nuvation Bio Inc.

A Phase 3, Multicenter, Clinical Study to Evaluate the Efficacy and Safety of Safusidenib Erbumine in Participants With Isocitrate Dehydrogenase 1 (IDH1)-Mutant Glioma

This is a 3-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 2 or Grade 3 astrocytoma with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double-blind, and placebo-controlled.

The purpose of Part 3 will be to evaluate the efficacy of safusidenib in participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma who have received surgery as their only treatment. Part 3 will be an open-label single-arm cohort and will enroll participants concurrently with Part 2.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Part 1 was fully enrolled as of 19 Dec 2023 and participants are currently ongoing.

Part 2 will include approximately 300 participants with IDH1-mutant Grade 2 or Grade 3 astrocytoma 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.

Part 3 will include approximately 40 participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma with measurable disease who have undergone surgery as their only treatment and are not in need of immediate chemotherapy or radiotherapy. Participants will receive oral safusidenib 250 mg BID in 28-day continuous cycles until disease progression or another reason for discontinuation occurs.

Study Type

Interventional

Enrollment (Estimated)

365

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia
        • Recruiting
        • St Vincents Hospital Sydney (Kinghorn)
        • Contact:
        • Principal Investigator:
          • Subotheni Thavaneswaran, MD
      • Saint Leonards, New South Wales, Australia
        • Not yet recruiting
        • Royal North Shore Hospital
        • Principal Investigator:
          • Helen Wheeler, MD
        • Contact:
    • Queensland
      • Herston, Queensland, Australia
        • Recruiting
        • Royal Brisbane and Women's Hospital
        • Principal Investigator:
          • Zarnie Lwin, MD
        • Contact:
    • Victoria
      • Melbourne, Victoria, Australia
        • Recruiting
        • Peter MacCallum Cancer Centre
        • Principal Investigator:
          • Jim Whittle, MD
        • Contact:
      • Melbourne, Victoria, Australia
        • Recruiting
        • The Alfred
        • Contact:
        • Principal Investigator:
          • Lucy Gately, MD
  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100070
        • Recruiting
        • Beijing Tiantan Hospital, Capital Medical University
        • Contact:
        • Principal Investigator:
          • Xiaohui Ren, MD
      • Beijing, Beijing Municipality, China, 100730
        • Not yet recruiting
        • Peking Union Medical College Hospital
        • Contact:
        • Principal Investigator:
          • Wenbin Ma, MD
      • Beijing, Beijing Municipality, China, 100093
        • Recruiting
        • Sanbo Brain Hospital, Capital Medical University
        • Contact:
        • Principal Investigator:
          • Junping Zhang, MD
      • Beijing, Beijing Municipality, China, 10053
        • Recruiting
        • Xuanwu Hospital, Capital Medical University
        • Contact:
        • Principal Investigator:
          • Qingtang Lin, MD
    • Fujian
      • Fuzhou, Fujian, China, 350005
        • Recruiting
        • The First Affiliated Hospital of Fujian Medical University
        • Contact:
        • Principal Investigator:
          • Dezhi Kang, MD
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
        • Principal Investigator:
          • Zhongping Chen, MD
    • Hunan
      • Changsha, Hunan, China, 410008
        • Not yet recruiting
        • Xiangya Hospital of Central South University
        • Contact:
        • Principal Investigator:
          • Zhixiong Liu, MD
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200040
        • Recruiting
        • Huashan Hospital affiliated to Fudan University
        • Contact:
        • Principal Investigator:
          • Ying Mao, MD
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital of Sichuan University
        • Principal Investigator:
          • Yanhui Liu, MD
        • Contact:
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama
        • Contact:
        • Principal Investigator:
          • Luis Nabors, MD
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Recruiting
        • St. Joseph's Hospital and Medical Center
        • Principal Investigator:
          • Yoshie Umemura, MD
        • Contact:
      • Phoenix, Arizona, United States, 85013
        • Recruiting
        • Mayo Clinic - Arizona
        • Principal Investigator:
          • Shannon Fortin Ensign, MD
        • Contact:
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles
        • Contact:
        • Contact:
          • Phone Number: 310-206-6909
        • Principal Investigator:
          • Robert Chong, MD
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Hoag Memorial Hospital Presbyterian
        • Principal Investigator:
          • Simon Khagi, MD
        • Contact:
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University
        • Principal Investigator:
          • Seema Nagpal, MD
        • Contact:
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California
        • Principal Investigator:
          • John De Groot, MD
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Not yet recruiting
        • University of Colorado Health Cancer Care
        • Contact:
        • Principal Investigator:
          • Doug Ney, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale University
        • Principal Investigator:
          • Nicholas Blondin, MD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32608
        • Recruiting
        • University of Florida Health
        • Principal Investigator:
          • Ashley Ghiaseddin, MD
        • Contact:
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic - Florida
        • Principal Investigator:
          • Wendy Sherman, MD
        • Contact:
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Health
        • Principal Investigator:
          • Macarena De La Fuente, MD
        • Contact:
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health Cancer Institute
        • Principal Investigator:
          • Alfredo Voloschin, MD
        • Contact:
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Principal Investigator:
          • Tolga Tuncer, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • David Reardon, MD
        • Contact:
      • Boston, Massachusetts, United States, 02214
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Julie Miller, M.D.
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Principal Investigator:
          • Tobias Walbert, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic - Rochester
        • Contact:
        • Principal Investigator:
          • Eva Galanis, MD
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Principal Investigator:
          • Omar Butt, MD
        • Contact:
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute
        • Contact:
        • Principal Investigator:
          • Morana Vojnic, MD
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health
        • Contact:
        • Principal Investigator:
          • Jose McFaline-Figueroa, MD
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Thomas Kaley, M.D.
        • Contact:
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Principal Investigator:
          • Fabio Iwamoto, MD
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke Cancer Institute
        • Principal Investigator:
          • Katy Peters, M.D.
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • Mina Lobbous, M.D.
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
        • Principal Investigator:
          • Michael Youssef, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Vinay Puduvalli, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • UVA Health, Emily Couric Clinical Cancer Cente
        • Principal Investigator:
          • David Schiff, M.D.
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • Fred Hutch Cancer Center
        • Principal Investigator:
          • Vyshak Venur, MD
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Health
        • Principal Investigator:
          • Ankush Bhatia, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria for Part 1:

  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.
  3. 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.
  4. Patient has received no more than 2 prior therapies for disease recurrence/progression.
  5. Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
  6. 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.

Key Inclusion Criteria for Part 2 and 3:

  1. Must be ≥18 years old at the time of signing the ICF.
  2. 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.
  3. Has adequate hematologic and organ function

Key Inclusion Criteria for Part 2:

  1. Diagnosis of histologically confirmed IDH1-mutant Grade 2, Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.
  2. 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.
  3. Must not have experienced tumor recurrence or progression between first day of radiotherapy and randomization by local assessment per RANO 2.0.
  4. Participants must have completed radiation therapy with a minimum of 80% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant . Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide.

Key Inclusion Criteria for Part 3:

  1. Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, or gross total resection), with the most recent surgery having occurred at least 90 days and no longer than 5 years before the date of enrollment, have not had any other prior anticancer therapy, including chemotherapy and radiotherapy, and are not in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
  2. Have histologically confirmed Grade 3 IDH-mutant oligodendroglioma according to WHO 2021 criteria per local assessment.
  3. Have residual or recurrent measurable disease per RANO 2.0 and confirmed by BICR, at the time of enrollment.
  4. Have an IDH1 mutation (R132H/C/G/S/L). The presence of 1p19q co-deletion must also be confirmed. All results must be generated using a validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory.

Key Exclusion Criteria for Part 1:

  1. Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
  2. Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
  3. Surgery: within 3 weeks
  4. Radiation therapy: within 12 weeks
  5. Investigational agents: within 5 half-lives for other investigational agents
  6. Patient did receive the prior therapy targeted to IDH1 mutation..
  7. Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.

Key Exclusion Criteria for Part 2 and 3:

  1. 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.
  2. Have brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension.
  3. Significant functional or neurocognitive deficits, including uncontrolled seizures, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
  4. Evidence of diffuse leptomeningeal disease.
  5. History of significant cardiac disease within 12 months prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
  6. If taking corticosteroids, must be on a stable or decreasing dose for the 14 days prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
  7. Participants with other malignancies must have received curative treatment and been disease-free for at least 3 years. Curatively resected skin cancer or curatively treated carcinoma in situ is allowed.
  8. Have a condition that would interfere with, or increase the risk of, study participation.

Key Exclusion Criteria for Part 2 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.

Key Exclusion Criteria for Part 3:

1. Participants may not have received any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including radiotherapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • DS-1001b
  • AB-218
Experimental: 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.
Drug: 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.
Other Names:
  • DS-1001b
  • AB-218
Experimental: 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.
Drug: 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.
Other Names:
  • DS-1001b
  • AB-218
Experimental: 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.
Drug: 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.
Other Names:
  • DS-1001b
  • AB-218
Experimental: 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.
Drug: 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.
Other Names:
  • DS-1001b
  • AB-218
Experimental: 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.
Drug: 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.
Other Names:
  • DS-1001b
  • AB-218
Placebo Comparator: 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.
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.
Experimental: safusidenib 250mg bid (Part 3)
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.
Drug: 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.
Other Names:
  • DS-1001b
  • AB-218

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: 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 treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed by CTCAE 5.0
From participants sign ICF to 30 days after last dose，average 2 years
Part 2: Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) per Response Assessment in Neuro-Oncology (RANO) 2.0
Time Frame: From randomization until the date of first documented disease progression, average 2 years
PFS is defined as the time from randomization to the date of the first documented disease progression assessed by BICR per RANO 2.0 or death (by any cause in the absence of disease progression).
From randomization until the date of first documented disease progression, average 2 years
Part 3 Objective Response Rate (ORR) (Complete Response (CR), Partial Response (PR) and Minor Response (MR)) assessed by Blinded Independent Central Review (BICR) per Response Assessment in Neuro-Oncology (RANO) 2.0
Time Frame: From the first dose of study drug until the date of first documented disease progression, average 18 months
From the first dose of study drug until the date of first documented disease progression, average 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Cmax of safusidenib
Time Frame: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Peak Plasma Concentration (Cmax)
on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1: Tmax of safusidenib
Time Frame: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
the time for safusidenib to reach Cmax
on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1: AUC8h of safusidenib
Time Frame: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Area under the plasma concentration curve (AUC) from time 0 to 8 hours
on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1 : AUC12h of safusidenib
Time Frame: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Area under the plasma concentration curve (AUC) from time 0 to 12 hours
on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1: AUC24h [QD only] of safusidenib
Time Frame: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Area under the plasma concentration curve (AUC) from time 0 to 24h hours for 500mg qd cohort
on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1 : Ctrough of safusidenib
Time Frame: on Days 2, 3, 4, 6, 8, 9 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 6 and 8 (every cycle is 28 days)
Lowest plasma concentration reached after AB-218 administration
on Days 2, 3, 4, 6, 8, 9 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 6 and 8 (every cycle is 28 days)
Part 1: Overall Response Rate (ORR) assessed by the investigator
Time Frame: from the first dose of study drug until the date of first documented disease progression, average 2 years
ORR (defined as the proportion of participants with the best overall confirmed response of Complete Response (CR), Partial Response (PR) or Minor Response (MR)[for RANO-HGG/RANO LGG] according to the appropriate tumor response criteria) as assessed by the Investigator
from the first dose of study drug until the date of first documented disease progression, average 2 years
Part 1: Duration of Response (DOR) assessed by the Investigator
Time Frame: from the first dose of study drug until the date of first documented disease progression, average 2 years
DOR, defined as the time from the first documentation of objective response (CR, PR, or MR) to the date of the first documentation of disease progression per RANO-HGG/RANO-LGG as applicable, or death (by any cause in the absence of progression), for participants with confirmed objective response, as assessed by the Investigator
from the first dose of study drug until the date of first documented disease progression, average 2 years
Part 1: Disease control rate (DCR) assessed by the Investigator
Time Frame: from the first dose of study drug until the date of first documented disease progression, average 2 years
DCR, defined as the proportion of patients with a best overall response of CR, PR, Stable Disease (SD), or Minor Response (MR) per RANO-HGG/RANO-LGG as applicable, as assessed by the Investigator
from the first dose of study drug until the date of first documented disease progression, average 2 years
Part 1: Progression free survival (PFS) assessed by the Investigator
Time Frame: from the first dose of study drug until the date of first documented disease progression, average 2 years
PFS, defined as the time from the first dose of study drug to the date of the first documented disease progression per RANO-HGG/RANO-LGG as applicable, or death (by any cause in the absence of disease progression), as assessed by the Investigator
from the first dose of study drug until the date of first documented disease progression, average 2 years
Part1: Time to Response (TTR) assessed by the Investigator.
Time Frame: From the first dose of study drug until the date of first documented objective response, average 2 years
TTR, the time from the first dose of study drug to the first documentation of objective response (CR, PR, or MR) per RANO-HGG/RANO-LGG as applicable, for participants with confirmed objective response, as assessed by the Investigator.
From the first dose of study drug until the date of first documented objective response, average 2 years
Part 1: Overall Survival (OS)
Time Frame: from the first dose of study drug to date of death, average 7 years
OS, defined as the time from randomization to death from any cause. Participants without death information at the analysis cutoff date will be censored at last date known to be alive.
from the first dose of study drug to date of death, average 7 years
Part2: DCR assessed by BICR and by the Investigator
Time Frame: from randomization until the date of first documented disease progression, average 2 years
DCR, defined as the proportion of participants with a best overall response of CR, PR, MR, or SD per RANO 2.0, as assessed by the Investigator and BICR
from randomization until the date of first documented disease progression, average 2 years
Part2: ORR
Time Frame: from randomization until the date of first documented disease progression, average 2 years
ORR, defined as the proportion of participants with the confirmed best overall response of CR, PR, or MR per RANO 2.0, as assessed by BICR and the Investigator.
from randomization until the date of first documented disease progression, average 2 years
Part2: DOR, assessed by BICR and the Investigator
Time Frame: from randomization until the date of first documented disease progression, average 2 years
DOR, the time from the first documentation of objective response (CR, PR, or MR) to the date of the first documentation of disease progression RANO 2.0, or death (by any cause in the absence of progression), for participants with confirmed objective response, as assessed by the BICR and the Investigator.
from randomization until the date of first documented disease progression, average 2 years
Part2: Time to Response (TTR) assessed by BICR and by the Investigator
Time Frame: From randomization until the date of first documented objective response, average 2 years
TTR, defined as the time from randomization to the first documentation of objective response (CR, PR, or MR) per RANO 2.0, for participants with confirmed objective response, as assessed by the BICR and the Investigator.
From randomization until the date of first documented objective response, average 2 years
Part2: Time to Next Intervention (TTNI) by Investigator assessment
Time Frame: From randomization until the date of next treatment, average 2 years
TTNI, defined as the time from randomization to initiation of the first new anticancer therapy, or death due to any cause, whichever comes earlier. Participants who neither initiated new anticancer therapy nor have died at the analysis cutoff date will be censored at the last date known to be alive.
From randomization until the date of next treatment, average 2 years
Part2: Health-related quality of life
Time Frame: From the first dose of study drug to treatment discontinuation, average 2 years
The Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire
From the first dose of study drug to treatment discontinuation, average 2 years
Part2: Safety and tolerability
Time Frame: from the first dose of study drug until 30 days after treatment discontinuation, average 2 years
AEs graded by NCI CTCAE v5.0, laboratory abnormalities as graded by NCI CTCAE v5.0, vital signs, physical examinations, and ECGs.
from the first dose of study drug until 30 days after treatment discontinuation, average 2 years
Part2: Seizure Activity
Time Frame: from the first dose of study drug until the date of first documented disease progression, average 2 years
Defined as seizure frequencies and severity including type of seizure, seizure-related AEs, and changes in anti-epileptic medications.
from the first dose of study drug until the date of first documented disease progression, average 2 years
Part2: Safusidenib PK Profile
Time Frame: from the first dose of study drug through 20 weeks
Defined as safusidenib concentrations and PK parameters.
from the first dose of study drug through 20 weeks
Part 2: Overall Survival (OS)
Time Frame: from randomization to date of death, average 7 years
OS, defined as the time from randomization to death from any cause.
from randomization to date of death, average 7 years
Part 2: PFS assessed by the Investigator.
Time Frame: from randomization until the date of first documented disease progression, average 2 years
PFS, defined as the time from randomization to the date of the first documented disease progression per RANO 2.0, or death (by any cause in the absence of disease progression), as assessed by the Investigator.
from randomization until the date of first documented disease progression, average 2 years
Part 3: ORR, assessed by the Investigator
Time Frame: From first dose of study drug until the date of first documented disease progression, average 18 months
ORR, defined as the proportion of participants with the confirmed best overall response of CR, PR, or MR per RANO 2.0, as assessed by the Investigator.
From first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: DOR, assessed by BICR and the Investigator
Time Frame: From the first dose of study drug until the date of first documented disease progression, average 18 months
DOR, the time from the first documentation of objective response (CR, PR, or MR) to the date of the first documentation of disease progression per RANO 2.0, or death (by any cause in the absence of progression), as assessed by the BICR and the Investigator.
From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: Time to Next Intervention (TTNI)
Time Frame: From the first dose of study drug until the date of next treatment, average 18 months
TTNI, defined as the time from the first dose of study drug to initiation of the first subsequent anticancer therapy.
From the first dose of study drug until the date of next treatment, average 18 months
Part 3: PFS assessed by BICR and the Investigator.
Time Frame: From the first dose of study drug until the date of first documented disease progression, average 18 months
PFS, defined as the time from the first dose of study drug to the date of the first documented disease progression per RANO 2.0, or death (by any cause in the absence of disease progression), as assessed by BICR and the Investigator.
From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: DCR assessed by BICR and by the Investigator
Time Frame: From the first dose of study drug until the date of first documented disease progression, average 18 months
DCR, defined as the proportion of participants with a best overall response of CR, PR, MR, or SD per RANO 2.0, as assessed by the Investigator and BICR
From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: Time to Response (TTR) assessed by BICR and by the Investigator
Time Frame: From the first dose of study drug until the date of first documented disease progression, average 18 months
TTR, defined as the time from the first dose of study drug to the first documentation of objective response (CR, PR, or MR) per RANO 2.0, as assessed by the BICR and the Investigator.
From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: Overall Survival (OS)
Time Frame: From the first dose of study drug until the date of death, average 7 years
OS, defined as the time from the first dose of study drug to death from any cause.
From the first dose of study drug until the date of death, average 7 years
Part 3: Safety and tolerability
Time Frame: From the first dose of study drug until 30 days after treatment discontinuation, average 18 months
AEs graded by NCI CTCAE v5.0, laboratory abnormalities as graded by NCI CTCAE v5.0, vital signs, physical examinations, and ECGs.
From the first dose of study drug until 30 days after treatment discontinuation, average 18 months
Part 3: Safusidenib PK Profile
Time Frame: From the first dose of study drug through 20 weeks
Defined as safusidenib concentrations and PK parameters.[Time Frame: from the first dose of study drug through 20 weeks]
From the first dose of study drug through 20 weeks
Part 3: Health-related quality of life
Time Frame: From the first dose of study drug to treatment discontinuation, average 18 months
The Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Quality of Life in Epilepsy (QOLIE-10-P) questionnaires.
From the first dose of study drug to treatment discontinuation, average 18 months
Part 3: Seizure Activity
Time Frame: From the first dose of study drug until the date of first documented disease progression, average 18 months
Defined as seizure frequencies and severity including type of seizure, seizure-related AEs, and changes in anti-epileptic medications.
From the first dose of study drug until the date of first documented disease progression, average 18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
for part 1 stage 2 surgical participants: Safusidenib concentrations in both plasma and tumor tissues
Time Frame: in the 5th week after first safusidenib dose
The concentration of safusidenib in tumor tissue samples collected at the time of tumor resection and plasma samples.
in the 5th week after first safusidenib dose
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 safusidenib dose
The concentration of 2-HG in tumor tissue samples at the time of tumor resection posttreatment and in tumor tissue samples submitted pretreatment.
at the time of pre-treatment, and in the 5th week after first safusidenib dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nuvation Bio Inc.

Collaborators

AnHeart Therapeutics Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2023

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

March 13, 2022

First Submitted That Met QC Criteria

March 21, 2022

First Posted (Actual)

March 31, 2022

Study Record Updates

Last Update Posted (Actual)

March 5, 2026

Last Update Submitted That Met QC Criteria

March 3, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AB-218-G203

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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