Safety and Efficacy Study of Safusidenib in Participants With Grade 2 IDH1-Mutant Glioma

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Safusidenib in Participants With Grade 2 Isocitrate Dehydrogenase 1 (IDH1)-Mutant Glioma

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study comparing the efficacy and safety of safusidenib versus placebo in participants with residual or recurrent Grade 2 glioma (oligodendroglioma or astrocytoma) with an IDH1 mutation who have undergone surgery as their only treatment and are not in need of immediate chemotherapy or radiotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Oligodendroglioma; IDH-mutant Gliomas; Astrocytoma IDH Mutant Grade 2; Grade 2 Glioma (Astrocytoma or Oligodendroglioma) With an IDH1 Mutation; Oligodendroglioma IDH-mutant and 1p/19q-codeleted
• Intervention / Treatment: Drug: Safusidenib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials at Nuvation Bio; Phone Number: 332-208-6102; Email: ClinicalTrials@nuvationbio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Expected survival of ≥12 months.
• 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 (or at least 28 days if biopsy only and postoperative changes have resolved per BICR) and no longer than 5 years before the date of randomization
• 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.
• Histologically confirmed Grade 2, IDH1-mutant oligodendroglioma or astrocytoma according to World Health Organization Central Nervous System 2021 classification criteria per Investigator assessment.
• IDH1 mutation (R132H/C/G/S/L), identified by polymerase chain reaction, next-generation sequencing (NGS), or immunohistochemistry; and confirmed 1p19q codeletion status by fluorescence in situ hybridization, NGS, or array comparative genomic hybridization.
• Residual or recurrent, measurable, non-enhancing disease, as confirmed by BICR per RANO 2.0, assessed at Screening.
• Adequate hematologic and organ functions

Key Exclusion Criteria:

• Any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including chemotherapy, investigational therapies, prior therapies targeting IDH1 or IDH2, anti-angiogenic therapies, tumor-treating fields, or radiotherapy.
• High-risk features as assessed by the Investigator, including brainstem or spinal cord involvement either as primary location or by significant tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with ability to comply with protocol requirements).
• Evidence of leptomeningeal disease.
• Use of therapeutic doses of steroids for signs/symptoms of glioma. Participants taking physiologic doses (defined as equivalent of <1.5 mg of dexamethasone equivalent) for medical conditions not related to glioma will be permitted.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo BID	Drug: Placebo; Placebo administered twice daily as a single agent dosed orally on Days 1 through 28 of a 28-day cycle. Participants may continue treatment with placebo until disease progression or another reason for discontinuation occurs.
Experimental: Safusidenib; Safusidenib 250 mg BID	Drug: Safusidenib; Safusidenib administered twice daily as a single agent dosed orally on Days 1 through 28 of a 28-day cycle. Participants may continue treatment until disease progression or another reason for discontinuation occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) per modified Response Assessment in Neuro-Oncology (RANO) 2.0	PFS, defined as time from date of randomization to the date of the first occurrence of radiographic disease progression per modified RANO 2.0 assessed by BICR or death from any cause, whichever occurs earlier	From the date of randomization until the date of first documented disease progression, approximately 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) assessed by BICR per modified RANO 2.0	ORR, defined as the proportion of participants with the confirmed best overall response of Complete Response (CR), Partial Response (PR), or Minor Response (MR) per modified RANO 2.0 assessed by BICR	From the date of randomization until the date of first documented disease progression, approximately 30 months
Time to Next Intervention (TTNI)	TTNI, defined as the time from randomization to the initiation of first subsequent anticancer therapy or death from any cause, whichever occurs earlier.	From the date of randomization until the date of the start of another anticancer treatment or date of death, approximately 30 months
PFS assessed by the Investigator per modified RANO 2.0	PFS, defined as the time from date of randomization to the date of the first occurrence of radiographic disease progression per modified RANO 2.0 assessed by the Investigator or death from any cause, whichever occurs earlier	From the date of randomization until the date of first documented disease progression, approximately 30 months
ORR assessed by the Investigator per modified RANO 2.0	ORR, defined as the proportion of participants with the confirmed best overall response of CR, PR, and MR per modified RANO 2.0 as assessed by the investigator.	From the date of randomization until the date of the first documented disease progression, approximately 30 months
Duration of Response (DOR) assessed by BICR and by the Investigator per modified RANO 2.0	DOR, the time from the first documentation of objective response (CR, PR, or MR) to the date of the first occurrence of radiographic disease progression per modified RANO 2.0 or death from any cause, whichever occurs earlier, as assessed by BICR and by the Investigator.	From the date of randomization until the date of first documented disease progression, approximately 30 months
Time to Response (TTR) assessed by BICR and by the Investigator per modified RANO 2.0	TTR, defined as the time from randomization to the first documentation of objective response (CR, PR, or MR) per modified RANO 2.0 assessed by BICR and by the Investigator.	From randomization to the first documentation of objective response (CR, PR, or MR), approximately 30 months
Disease Control Rate (DCR) assessed by BICR and by the Investigator per modified RANO 2.0	DCR, defined as the proportion of participants with a best overall response of CR, PR, MR, or stable disease (SD) per modified RANO 2.0, as assessed by BICR and by the Investigator	From the date of randomization until the date of first documented disease progression, approximately 30 months
Tumor Growth Rate (TGR) by volume assessed by BICR	TGR defined as the percentage change in tumor volume by unit of time, assessed by BICR	From historical scans through the final scan in the study, approximately 30 months
Overall Survival (OS)	OS, defined as the time from randomization to death from any cause	From the date of randomization until the date of death, approximately 30 months
Safety and tolerability	The safety and tolerability of safusidenib compared with placebo evaluated based on AEs graded by NCI-CTCAE version 5.0, laboratory abnormalities as graded by NCI-CTCAE version 5.0, vital signs, physical examinations, and ECGs	From the first dose of study drug until 30 days after treatment discontinuation, approximately 30 months
Safusidenib PK Profile	Characterize the safusidenib concentrations	From the first dose of study drug through approximately 16 weeks
Health-Related Quality of Life	Evaluate health-related quality of life (HRQoL) with safusidenib compared with placebo assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire scores.	From the first dose of study drug to treatment discontinuation, approximately 30 months
Health-Related Quality of Life	Evaluate health-related quality of life (HRQoL) with safusidenib compared with placebo assessed by the Quality of Life in Epilepsy (QOLIE-10-P) scores.	From the first dose of study drug to treatment discontinuation, approximately 30 months
Health-Related Quality of Life	Evaluate health-related quality of life (HRQoL) with safusidenib compared with placebo assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire scores.	From the first dose of study drug to treatment discontinuation, approximately 30 months
Seizure Activity	Evaluate seizure frequencies and severity including type of seizure, seizure-related AEs, and changes in anti-epileptic medications in participants receiving safusidenib compared with placebo	From the date of randomization until the date of first documented disease progression, approximately 30 months

Collaborators and Investigators

• Sponsor: Nuvation Bio Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): March 1, 2032

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: safusidenib; IDH1-mutant Glioma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Astrocytoma; Oligodendroglioma
• Other Study ID Numbers: NUV-218-G307

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