Safusidenib for Patients With Newly Diagnosed IDH1-mutant CNS WHO Grade 3 Oligodendroglioma and Astrocytoma - a Single Arm Phase II Study

NCT07832123 | Not Yet Recruiting Phase 2

• 1 other identifier: UZurich
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The precise positioning of the emerging group of pharmacological inhibitors of mutant IDH enzymes remains to be refined by further studies and defined in national and international guidelines. The present study shall help to close this important knowledge gap when trying to define the role of mutant IDH inhibitors in the treatment algorithms for patients with IDH-mutant WHO grade 3 gliomas. Safusidenib is a novel, oral, potent, brain penetrant inhibitor of mutant IDH1. It has shown high blood brain barrier penetration in both pre-clinical and clinical studies and demonstrated anti-tumor activity with complete or partial responses. We aim at demonstrating the efficacy of safusidenib in patients with newly diagnosed IDH1-mutant CNS WHO grade 3 oligodendroglioma and astrocytoma, measured by progression-free survival at12 months.

Conditions

Glioma : Oligodendroglioma or Astrocytoma

Keywords

glioma; oligodendroglioma; astrocytoma; WHO grade 3; IDH inhibitor; safusidenib

Outcome Measures

Primary Outcomes (1)

• progression-free survival at12 months

  progression-free survival at 12 months measured by central review of MRI

  12 months

Secondary Outcomes (8)

• Objective response to treatment in patients with measurable disease

  24 months

• Progression-free survival at 24 months

  24 months

• Median progression-free survival

  48 months

• Safety

  48 months

• Seizure control

  48 months

Other Outcomes (3)

• Volumetric response

  48 monts

• Response of 2-hydroxyglutarate levels by MR spectroscopy

  48 months

• Response to treatment assessed by positron emission tomography (PET)

  48 months

Study Arms (1)

Safusidenib arm

EXPERIMENTAL

All participants will receive safusidenib (250 mg BID) until progression or unacceptable toxicity.

Drug: Safusidenib

Interventions

Safusidenib DRUG

All participants will receive safusidenib (250 mg BID) until progression or unacceptable toxicity.

Safusidenib arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥18 years.
• Newly diagnosed and histologically confirmed IDH1-mutant WHO grade 3 glioma, without or with residual disease: astrocytoma IDH1-mutant, or oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, CNS WHO grade 3. IDH1 mutation can be defined by immunohistochemistry or by sequencing. Any location in the central nervous system is permitted.
• Karnofsky performance status of 70 or more.
• Adequate hematologic and organ functions.
• If taking corticosteroids, patients must be on a stable or decreasing dose for the 14 days prior first dose of study drug.
• Female patients must be either documented not to be Women of Childbearing Potential (WOCBP) or must have a negative pregnancy test within 14 days of starting treatment. Additionally WOCBP must agree to use, from the screening to at least 90 days following the last administration of safusidenib, highly effective contraception methods. Male subjects able to father children must agree to use two acceptable methods of contraception throughout the study and during at least 90 days following the last administration of safusidenib (e.g., condom with spermicidal gel). Double-barrier contraception is required.
• Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
• Written informed consent for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.

You may not qualify if:

• Inability to undergo brain or spine MRI.
• Intent to be treated with radiotherapy or alkylating agent chemotherapy.
• Any investigational antitumor therapy other than those under investigation in this study.
• Any severe concomitant condition including active and uncontrolled infections or other severe concurrent disease, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.
• Known hypersensitivity to safusidenib, to any drug with similar chemical structure, or to any other excipient present in the pharmaceutical form of safusidenib.
• Subjects with a corrected QT interval by Fredericia's formula (QTcF) ≥470 milliseconds (msec) or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome).
• Subjects with history of significant cardiac disease within 12 months prior to first dose of study drug.
• Subjects with known human immunodeficiency virus (HIV) are ineligible unless the following criteria are met: have been receiving effective antiretroviral therapy for at least 4 weeks; viral load \<400 copies/mL, CD4+ T-cell (CD4+) counts ≥350 cells/μL, an absence of opportunistic infections for the last 12 months, and participant agrees to be treated with anti-viral therapy for the duration of the study, if indicated.
• Subjects with acute or reactivated hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Judgment by the investigator that the patient should not participate in the study because the patient is unlikely to comply with study procedures, restrictions and requirements. Only patients capable of judgment can be enrolled.
• Pregnancy or intention to become pregnant during the course of the study. WOCBP potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test.
• Women who are breast feeding and who do not agree to discontinue nursing prior to the first study treatment and for the period defined in the protocol.
• Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
• Concurrent malignancies unless the patient has been disease-free without intervention for at least one year.
• Concurrent use of other anti-cancer treatments or agents other than study medication.

Sponsors & Collaborators

• University of Zurich: lead
• Nuvation Bio Inc.: collaborator
• University Hospital, Zürich: collaborator

Study Sites (1)

University Hospital Zürich

Zurich, Canton of Zurich, Switzerland

Location

Related Publications (2)

• Drummond KJ, Spiteri M, Cain SA, Jones J, Shaya S, Topp M, Lu T, Tobler R, Valkovic AL, Moore Z, Fatunla OE, Kriel J, Moffet JJD, McAlpine H, Rosier M, Guan H, Dimou J, Schadewaldt V, Roberts-Thomson S, McArdle D, Lui E, Voelker-Albert M, di Sanzo S, Nijagal B, Narayana VK, Mitchell CB, Vissers JHA, Grimmond S, Rosenthal MA, Palmer LM, Best SA, Freytag S, Whittle JR. Perioperative IDH inhibition in treatment-naive IDH-mutant glioma: a pilot trial. Nat Med. 2025 Oct;31(10):3451-3463. doi: 10.1038/s41591-025-03884-4. Epub 2025 Aug 21.

  PMID: 40841487 BACKGROUND

• Arakawa Y, Saito R, Kanemura Y, Mishima K, Koriyama S, Narita Y, Kumabe T, Motomura K, Sugiyama K, Yamasaki F, Mukasa A, Kanamori M, Kuga D, Nagane M, Kakurai Y, Isobe K, Nakamura H. Phase II study of safusidenib erbumine in patients with chemotherapy- and radiotherapy-naive isocitrate dehydrogenase 1-mutated WHO grade 2 gliomas. Neuro Oncol. 2026 Mar 1;28(3):717-727. doi: 10.1093/neuonc/noaf258.

  PMID: 41206766 BACKGROUND

MeSH Terms

Conditions

Astrocytoma; Glioma; Oligodendroglioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Michael Weller, MD

  University of Zurich

  STUDY CHAIR

Central Study Contacts

Emilie Le Rhun, MD PhD

CONTACT

+41 44 255 55 00; emilie.lerhun@usz.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-09

Locations

CH (1)