Astrocytoma IDH Mutant Grade 2, Grade 2 Glioma (Astrocytoma or Oligodendroglioma) With an IDH1 Mutation, IDH-mutant Gliomas, Oligodendroglioma, Oligodendroglioma IDH-mutant and 1p/19q-codeleted
Conditions
Keywords
safusidenib, IDH1-mutant Glioma
Brief summary
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study comparing the efficacy and safety of safusidenib versus placebo in participants with residual or recurrent Grade 2 glioma (oligodendroglioma or astrocytoma) with an IDH1 mutation who have undergone surgery as their only treatment and are not in need of immediate chemotherapy or radiotherapy.
Interventions
DRUGSafusidenib
Safusidenib administered twice daily as a single agent dosed orally on Days 1 through 28 of a 28-day cycle. Participants may continue treatment until disease progression or another reason for discontinuation occurs.
DRUGPlacebo
Placebo administered twice daily as a single agent dosed orally on Days 1 through 28 of a 28-day cycle. Participants may continue treatment with placebo until disease progression or another reason for discontinuation occurs.
Sponsors
Nuvation Bio Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Sponsor and Sponsor representatives (including the CRO) will be blinded to the treatment assignment.
Intervention model description
Randomized, double-blind, placebo-controlled with the possibility for crossover for participants receiving placebo should they meet specific eligibility requirements.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) per modified Response Assessment in Neuro-Oncology (RANO) 2.0 | From the date of randomization until the date of first documented disease progression, approximately 30 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) assessed by BICR per modified RANO 2.0 | From the date of randomization until the date of first documented disease progression, approximately 30 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 |
| Time to Next Intervention (TTNI) | From the date of randomization until the date of the start of another anticancer treatment or date of death, approximately 30 months | TTNI, defined as the time from randomization to the initiation of first subsequent anticancer therapy or death from any cause, whichever occurs earlier. |
| PFS assessed by the Investigator per modified RANO 2.0 | From the date of randomization until the date of first documented disease progression, approximately 30 months | 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 |
| ORR assessed by the Investigator per modified RANO 2.0 | From the date of randomization until the date of the first documented disease progression, approximately 30 months | 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. |
| Duration of Response (DOR) assessed by BICR and by the Investigator per modified RANO 2.0 | From the date of randomization until the date of first documented disease progression, approximately 30 months | 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 to Response (TTR) assessed by BICR and by the Investigator per modified RANO 2.0 | From randomization to the first documentation of objective response (CR, PR, or MR), approximately 30 months | 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. |
| Disease Control Rate (DCR) assessed by BICR and by the Investigator per modified RANO 2.0 | From the date of randomization until the date of first documented disease progression, approximately 30 months | 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 |
| Tumor Growth Rate (TGR) by volume assessed by BICR | From historical scans through the final scan in the study, approximately 30 months | TGR defined as the percentage change in tumor volume by unit of time, assessed by BICR |
| Overall Survival (OS) | From the date of randomization until the date of death, approximately 30 months | OS, defined as the time from randomization to death from any cause |
| Safety and tolerability | From the first dose of study drug until 30 days after treatment discontinuation, approximately 30 months | 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 |
| Safusidenib PK Profile | From the first dose of study drug through approximately 16 weeks | Characterize the safusidenib concentrations |
| Health-Related Quality of Life | From the first dose of study drug to treatment discontinuation, approximately 30 months | 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. |
| Seizure Activity | From the date of randomization until the date of first documented disease progression, approximately 30 months | 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 |
Contacts
CONTACTClinical Trials at Nuvation Bio
Outcome results
None listed