Home › Trials › NCT05303519

Safusidenib as maintenance therapy for IDH1‑mutant astrocytoma and oligodendroglioma

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

Phase 3 Interventional Nuvation Bio Inc. · NCT05303519

This trial tests whether the oral drug safusidenib can help people with IDH1‑mutant astrocytomas or oligodendrogliomas remain progression‑free longer after surgery and standard radiation/chemotherapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment365 (estimated)
Ages18 Years and up
SexAll
SponsorNuvation Bio Inc. Industry-sponsored
Drugs / interventionsbevacizumab, chemotherapy, radiation
Locations45 sites (Birmingham, Alabama and 44 other locations)
Trial IDNCT05303519 on ClinicalTrials.gov

What this trial studies

This is a three‑part Phase 3 interventional program of safusidenib in adults with IDH1‑mutant gliomas. Part 1 was a small dose‑finding cohort that characterized safety, pharmacokinetics, and initial activity across several oral dose levels in recurrent/progressive Grade 2–3 IDH1‑mutant glioma. Part 2 is a randomized, double‑blind, placebo‑controlled maintenance study (approximately 300 participants) comparing safusidenib 250 mg BID versus placebo after standard radiation/chemoradiation and adjuvant temozolomide in high‑risk Grade 2/3 astrocytoma or Grade 4 astrocytoma. Part 3 is an open‑label single‑arm cohort (about 40 participants) of safusidenib for residual or recurrent Grade 3 oligodendroglioma following surgery only, with tumor response assessed by blinded independent central review and long‑term survival follow‑up.

Who should consider this trial

Good fit: Adults (≥18) with confirmed IDH1 R132 mutations who fit the cohort definitions — recurrent/progressive Grade 2–3 glioma (Part 1), post‑radiation/temozolomide high‑risk Grade 2/3 or Grade 4 astrocytoma (Part 2), or residual/recurrent Grade 3 oligodendroglioma after surgery only (Part 3) — are the intended participants.

Not a fit: Patients without an IDH1 R132 mutation, those needing immediate chemotherapy or radiotherapy, or those who have had more than two prior therapies for recurrence are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, safusidenib could delay tumor progression and reduce the need for additional chemotherapy or radiation, potentially extending progression‑free and overall survival.

How similar studies have performed: IDH1 inhibitors have shown activity in other IDH‑mutant cancers and in early glioma studies, but large randomized Phase 3 evidence in glioma is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Birmingham, Alabama and 44 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions GliomaAstrocytoma, Grade IVIDH1-mutant GliomaAstrocytoma, IDH-Mutant, Grade 3Astrocytoma, IDH-Mutant, Grade 4Astrocytoma, IDH-Mutant, Grade 2OligodendrogliomaOligodendroglioma, IDH-Mutant and 1p/19q-Codeleted
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.