Title
A Phase 2, multicenter, clinical study to evaluate the efficacy and safety of safusidenib erbumine in patients with isocitrate dehydrogenase 1 (IDH1)-mutant glioma

Description
Part 1 of this study will enroll up to 25 patients that will be randomized 1:1:1:1:1 (5 patients per group) to receive one of the daily oral doses of safusidenib at 125 mg twice a day (BID), 250 mg BID, 500 mg once daily (QD), 375 mg BID, or 500 mg BID. The PK characteristics and safety and initial efficacy data will be assessed in Part 1.was fully enrolled as of 19 Dec 2023 and participants are currently ongoing.

Part 2 will include approximately 100 participants with IDH1-mutant astrocytoma, Grade 3 with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Participants will be randomized (1:1) after their last dose of adjuvant temozolomide to receive either oral safusidenib 250 mg BID or placebo in 28-day continuous cycles. Patients will continue treatment until progression of disease or until other discontinuation criteria are met. The tumor response evaluation will be conducted on a regular basis until progression of disease per Blinded Independent Central Review (BICR), consent withdrawal, or death, whichever occurs first. Long-term survival follow-up will be conducted as well.

Objective
Part 1:
Primary: To evaluate the safety and determine the RP2D of safusidenib in the treatment of recurrent/progressive IDH1-mutant WHO Grade 2/3 glioma.
Secondary: To evaluate the PK profile of safusidenib following oral administration.
To evaluate the efficacy of safusidenib in the treatment of recurrent/progressive IDH1-mutant WHO Grade 2/3 glioma.

Part 2: Primary -To evaluate the efficacy of maintenance safusidenib versus placebo in IDH1-mutant Grade 3 astrocytoma with high-risk features and Grade 4 astrocytoma following standard-of-care radiation or chemoradiation and adjuvant temozolomide
Secondary: To compare OS between safusidenib and placebo.
To evaluate the efficacy of safusidenib compared with placebo based on PFS by Investigator assessment.
To evaluate the efficacy of safusidenib and placebo based on DCR.
To evaluate the efficacy of safusidenib compared with placebo by ORR.
To evaluate the DOR of safusidenib compared with placebo.
To evaluate the efficacy of safusidenib and placebo based on TTR.
To evaluate the efficacy of safusidenib compared with placebo based on TTNI
To evaluate health-related quality of life with safusidenib compared with placebo as assessed by Patient-Reported Outcome questionnaires.
To evaluate the safety and tolerability of safusidenib compared with placebo.
To evaluate seizure activity in participants receiving safusidenib compared with placebo.
To evaluate the PK profile of safusidenib

Treatment This is a 2-part study. The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants with recurrent/progressive IDH1-mutant World Health Organization (WHO) Grade 2 or Grade 3 glioma.

The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 3 astrocytoma with high-risk features or Grade 4 IDH1-mutant astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double blind, and placebo controlled.

Key Eligibility For full study eligibility, see This study's ClinicalTrials.gov record.

Applicable Disease Sites
Brain/Central Nervous System

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital