Astrocytoma IDH Mutant Grade 2, Astrocytoma IDH Mutant Grade 3, Glioma, Grade 2 IDH1-mutant Glioma, Grade 3 IDH1-mutant Glioma, IDH1-mutant Glioma, Oligodendroglioma, Oligodendroglioma IDH-1 Mutant and 1/p19q-codeleted
Conditions
Brief summary
This study will include up to 40 participants with Grade 2 or Grade 3 IDH1-mutant glioma who have undergone surgery and received vorasidenib as their only treatment, experienced radiographic disease progression on vorasidenib (confirmed by Blinded Independent Central Review \[BICR\] per modified Response Assessment in Neuro-Oncology \[RANO\] 2.0), and are not in need of immediate chemotherapy or radiotherapy.
Interventions
DRUGSafusidenib
Safusidenib administered twice daily as a single agent orally on Days 1 to 28 of a 28-day cycle. Participants may continue treatment until disease progression or another reason for discontinuation occurs.
Sponsors
Nuvation Bio Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically confirmed Grade 2 or 3 IDH-mutant astrocytoma or IDH-mutant and 1p19q co-deleted oligodendroglioma, according to WHO CNS 2021 criteria * IDH1 mutation (e.g., R132H/C/G/S/L) based on immunohistochemistry (IHC) (R132H only), PCR, or next generation sequencing (NGS). * Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, or gross total resection). * Measurable disease per modified RANO 2.0 confirmed by BICR during Screening. * Previously treated with vorasidenib and experienced radiographic disease progression during treatment and are not in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator. Disease progression must be confirmed by BICR using modified RANO 2.0. * Adequate hematologic and organ function * Expected survival of ≥12 months Key
Exclusion criteria
* Any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) and vorasidenib for treatment of glioma. * Discontinued vorasidenib for toxicity or any reason other than radiographic disease progression * Prior treatment with anti-angiogenic agents such as Avastin (bevacizumab) or investigational agents for glioma. * Brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension. * Significant functional or neurocognitive deficits, including uncontrolled seizures * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) per modified Response Assessment in Neuro-Oncology (RANO) 2.0 assessed by Blinded Independent Central Review (BICR) | From the date of first dose of study drug until the date of first documented disease progression, approximately 18 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR per modified RANO 2.0 assessed by Investigator | From the date of first dose of study drug until the date of first documented disease progression, approximately 18 months | ORR defined as the proportion of participants with the confirmed best overall response of CR, PR or MR per modified RANO 2.0, assessed by the Investigator |
| Volumetric Tumor Growth Rate (TGR) by BICR | From historical scans through the final scan in the study, approximately 18 months | TGR defined as the percentage change in tumor volume by unit of time, assessed by BICR |
| Duration of Response (DOR) per modified RANO 2.0 assessed by BICR and by Investigator | From the date of first dose of study drug until the date of first documented disease progression, approximately 18 months | DOR, 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 assessed by BICR and by the Investigator or death from any cause, whichever occurs earlier. |
| Time to Next Intervention (TTNI) | From the date of first dose of study drug until the date of the start of another anticancer treatment or date of death, approximately 18 months | TTNI, defined as the time from the first dose of study drug to the initiation of first subsequent anticancer therapy or death from any cause, whichever occurs earlier |
| Progression Free Survival (PFS) per modified RANO 2.0 assessed by BICR and by Investigator | From the date of first dose of study drug until the date of first documented disease progression, approximately 18 months | PFS, defined as the time from the first dose of study drug to the date of the first occurrence of radiographic disease progression per modified RANO 2.0 assessed by BICR and by the Investigator or death from any cause, whichever occurs earlier. |
| Time to Response (TTR) per modified RANO 2.0 assessed by BICR and by Investigator | From the date of first dose of study drug to the first documentation of objective response (CR, PR, or MR), approximately 18 months | TTR, defined as the time from the first dose of study drug to the first documentation of objective response (CR, PR, or MR) per modified RANO 2.0, assessed by BICR and by the Investigator |
| Overall Survival (OS) | From the date of first dose of study drug until the date of death, approximately 18 months | OS, defined as the time from the first dose of study drug to death from any cause. |
| Safety and tolerability | From the date of first dose of study drug until 30 days after the date of the last dose of study drug, approximately 18 months | The safety and tolerability of safusidenib 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 |
| Seizure Activity | From the date of first dose of study drug until the date of first documented disease progression, approximately 18 months | Evaluate seizure frequencies and severity including type of seizure, seizure-related AEs, and changes in anti-epileptic medications in participants receiving safusidenib |
Countries
United States
Contacts
CONTACTClinical Trials at Nuvation Bio
Outcome results
None listed