Safusidenib Phase 2 Study in IDH1 Mutant Glioma
- Conditions
- GliomaAstrocytoma, Grade IVIDH1-mutant GliomaAstrocytoma, IDH-Mutant, Grade 3Astrocytoma, IDH-Mutant, Grade 4
- Interventions
- Drug: Placebo
- Registration Number
- NCT05303519
- Lead Sponsor
- Nuvation Bio Inc.
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 125
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description safusidenib 125mg bid (part 1) safusidenib safusidenib 125mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity. safusidenib 250mg bid (part 1) safusidenib safusidenib 250mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity. safusidenib 500mg qd (part 1) safusidenib safusidenib 500mg qd administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity. safusidenib 375mg bid (part 1) safusidenib safusidenib 375mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity. safusidenib 500mg bid (part 1) safusidenib safusidenib 500mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity. safusidenib 250mg bid (Part 2) safusidenib safusidenib administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment until disease progression or another reason for discontinuation occurs. placebo (Part 2) Placebo Placebo 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.
- Primary Outcome Measures
Name Time Method Part 1: Incidence of adverse events (AEs) and serious adverse events (SAEs) From participants sign ICF to 30 days after last dose，average 2 years 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 From randomization until the date of first documented disease progression, average 2 years 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).
- Secondary Outcome Measures
Name Time Method Part 1: Cmax of safusidenib on Cycle 1 Day 1 and Day 8 (every cycle is 28 days) Peak Plasma Concentration (Cmax)
Part 1: Tmax of safusidenib on Cycle 1 Day 1 and Day 8 (every cycle is 28 days) the time for safusidenib to reach Cmax
Part 1: AUC8h of safusidenib on Cycle 1 Day 1 and Day 8 (every cycle is 28 days) Area under the plasma concentration curve (AUC) from time 0 to 8 hours
Part 1 : AUC12h of safusidenib on Cycle 1 Day 1 and Day 8 (every cycle is 28 days) Area under the plasma concentration curve (AUC) from time 0 to 12 hours
Part 1: AUC24h [QD only] of safusidenib on Cycle 1 Day 1 and Day 8 (every cycle is 28 days) Area under the plasma concentration curve (AUC) from time 0 to 24h hours for 500mg qd cohort
Part 1 : Ctrough of safusidenib on Days 2, 3, 4, 6, 8, 9 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 6 and 8 (every cycle is 28 days) Lowest plasma concentration reached after AB-218 administration
Part 1: Overall Response Rate (ORR) assessed by the investigator from the first dose of study drug until the date of first documented disease progression, average 2 years ORR (defined as the proportion of participants with the best overall confirmed response of Complete Response (CR), Partial Response (PR) or Minor Response (MR)\[for RANO-HGG/RANO LGG\] according to the appropriate tumor response criteria) as assessed by the Investigator
Part 1: Duration of Response (DOR) assessed by the Investigator from the first dose of study drug until the date of first documented disease progression, average 2 years DOR, defined as the time from the first documentation of objective response (CR, PR, or MR) to the date of the first documentation of disease progression per RANO-HGG/RANO-LGG as applicable, or death (by any cause in the absence of progression), for participants with confirmed objective response, as assessed by the Investigator
Part 1: Disease control rate (DCR) assessed by the Investigator from the first dose of study drug until the date of first documented disease progression, average 2 years DCR, defined as the proportion of patients with a best overall response of CR, PR, Stable Disease (SD), or Minor Response (MR) per RANO-HGG/RANO-LGG as applicable, as assessed by the Investigator
Part 1: Progression free survival (PFS) assessed by the Investigator from the first dose of study drug until the date of first documented disease progression, average 2 years PFS, defined as the time from the first dose of study drug to the date of the first documented disease progression per RANO-HGG/RANO-LGG as applicable, or death (by any cause in the absence of disease progression), as assessed by the Investigator
Part1: Time to Response (TTR) assessed by the Investigator. From the first dose of study drug until the date of first documented objective response, average 2 years TTR, the time from the first dose of study drug to the first documentation of objective response (CR, PR, or MR) per RANO-HGG/RANO-LGG as applicable, for participants with confirmed objective response, as assessed by the Investigator.
Part 1: Overall Survival (OS) from the first dose of study drug to date of death, average 7 years OS, defined as the time from randomization to death from any cause. Participants without death information at the analysis cutoff date will be censored at last date known to be alive.
Part 2: Overall Survival (OS) from randomization to date of death, average 7 years OS, defined as the time from randomization to death from any cause. Participants without death information at the analysis cutoff date will be censored at last date known to be alive.
Part2: PFS assessed by the Investigator. from randomization until the date of first documented disease progression, average 2 years PFS, defined as the time from randomization to the date of the first documented disease progression per RANO 2.0, or death (by any cause in the absence of disease progression), as assessed by the Investigator.
Part2: DCR assessed by BICR and by the Investigator from randomization until the date of first documented disease progression, average 2 years DCR, defined as the proportion of participants with a best overall response of CR, PR, MR, or SD per RANO 2.0, as assessed by the Investigator and BICR
Part2: ORR from randomization until the date of first documented disease progression, average 2 years ORR, defined as the proportion of participants with the confirmed best overall response of CR, PR, or MR per RANO 2.0, as assessed by BICR and the Investigator.
Part2: DOR, assessed by BICR and the Investigator from randomization until the date of first documented disease progression, average 2 years DOR, the time from the first documentation of objective response (CR, PR, or MR) to the date of the first documentation of disease progression RANO 2.0, or death (by any cause in the absence of progression), for participants with confirmed objective response, as assessed by the BICR and the Investigator.
Part2: Time to Response (TTR) assessed by BICR and by the Investigator From randomization until the date of first documented objective response, average 2 years TTR, defined as the time from randomization to the first documentation of objective response (CR, PR, or MR) per RANO 2.0, for participants with confirmed objective response, as assessed by the BICR and the Investigator.
Part2: Time to Next Intervention (TTNI) by Investigator assessment From randomization until the date of next treatment, average 2 years TTNI, defined as the time from randomization to initiation of the first new anticancer therapy, or death due to any cause, whichever comes earlier. Participants who neither initiated new anticancer therapy nor have died at the analysis cutoff date will be censored at the last date known to be alive.
Part2: Health-related quality of life From the first dose of study drug to treatment discontinuation, average 2 years The Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire
Part2: Safety and tolerability from the first dose of study drug until 30 days after treatment discontinuation, average 2 years AEs graded by NCI CTCAE v5.0, laboratory abnormalities as graded by NCI CTCAE v5.0, vital signs, physical examinations, and ECGs.
Part2: Seizure Activity from the first dose of study drug until the date of first documented disease progression, average 2 years Defined as seizure frequencies and severity including type of seizure, seizure-related AEs, and changes in anti-epileptic medications.
Part2: Safusidenib PK Profile from the first dose of study drug through 20 weeks Defined as safusidenib concentrations and PK parameters.
Trial Locations
- Locations (9)
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Huntsman Cancer Insititute, University of Utah
🇺🇸Salt Lake City, Utah, United States
UVA Health, Emily Couric Clinical Cancer Cente
🇺🇸Charlottesville, Virginia, United States
St. Joseph's Hospital and Medical Center🇺🇸Phoenix, Arizona, United StatesResearch TeamContact(602) 406-8605Research@IvyBrainTumorCenter.orgYoshie Umemura, M.D.Principal Investigator