This is a 3-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 2 or Grade 3 astrocytoma with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double-blind, and placebo-controlled.
The purpose of Part 3 will be to evaluate the efficacy of safusidenib in participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma who have received surgery as their only treatment. Part 3 will be an open-label single-arm cohort and will enroll participants concurrently with Part 2.
Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
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.
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.
Patient has received no more than 2 prior therapies for disease recurrence/progression.
Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
Surgery: within 3 weeks
Radiation therapy: within 12 weeks
Investigational agents: within 5 half-lives for other investigational agents
Parallel
safusidenib
Drugsafusidenib administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with agent safusidenib until disease progression or development of other unacceptable toxicity.
Placebo
DrugPlacebo administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with placebo until disease progression or another reason for discontinuation occurs.
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Treatment groupsSee each treatment group below.
Part 1: Incidence of adverse events (AEs) and serious adverse events (SAEs)
calculate Percentage and numbers of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed by CTCAE 5.0
Part 2: Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) per Response Assessment in Neuro-Oncology (RANO) 2.0
PFS is defined as the time from randomization to the date of the first documented disease progression assessed by BICR per RANO 2.0 or death (by any cause in the absence of disease progression).
Part 3 Objective Response Rate (ORR) (Complete Response (CR), Partial Response (PR) and Minor Response (MR)) assessed by Blinded Independent Central Review (BICR) per Response Assessment in Neuro-Oncology (RANO) 2.0
Part 1: Cmax of safusidenib
Peak Plasma Concentration (Cmax)
Part 1: Tmax of safusidenib
the time for safusidenib to reach Cmax
Part 1: AUC8h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 8 hours
Part 1 : AUC12h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 12 hours
Click on the lead sponsor to view all of their trials.
Nuvation Bio Inc.
Lead sponsor
AnHeart Therapeutics Inc.
Collaborator
