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

Official title

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

Overview

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) per modified Response Assessment in Neuro-Oncology (RANO) 2.0 [Time frame: From the date of randomization until the date of first documented disease progression, approximately 30 months]

Secondary outcome measures (12)

• Objective Response Rate (ORR) assessed by BICR per modified RANO 2.0 [Time frame: From the date of randomization until the date of first documented disease progression, approximately 30 months]
• Time to Next Intervention (TTNI) [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: From historical scans through the final scan in the study, approximately 30 months]
• Overall Survival (OS) [Time frame: From the date of randomization until the date of death, approximately 30 months]
• Safety and tolerability [Time frame: From the first dose of study drug until 30 days after treatment discontinuation, approximately 30 months]
• Safusidenib PK Profile [Time frame: From the first dose of study drug through approximately 16 weeks]
• Health-Related Quality of Life [Time frame: From the first dose of study drug to treatment discontinuation, approximately 30 months]

Eligibility criteria

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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07712757 · NUV-218-G307

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗