NCT07712757 - Safety and Efficacy Study of Safusidenib in Participants With Grade 2 IDH1-Mutant Glioma | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

Time frame: From the date of randomization until the date of first documented disease progression, approximately 30 months

Secondary Outcomes

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

Time frame: 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.

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

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

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

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.

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

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.

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

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.

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

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

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

TGR defined as the percentage change in tumor volume by unit of time, assessed by BICR

Time frame: 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

Time frame: 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

Time frame: From the first dose of study drug until 30 days after treatment discontinuation, approximately 30 months

Safusidenib PK Profile

Characterize the safusidenib concentrations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: From the date of randomization until the date of first documented disease progression, approximately 30 months

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts