RECRUITING
Phase 3
ClinicalTrials.gov
SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)
Sponsor: Nuvation Bio Inc. • ClinicalTrials.gov ID: NCT05303519
Registry updated: 2026-10-19
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Check Eligibility →Description
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.
Interventions
-
safusidenib
(Drug)
safusidenib 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
(Drug)
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.
Eligibility criteria
Key Inclusion Criteria for Part 1:
1. Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. 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.
3. 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.
4. Patient has received no more than 2 prior therapies for disease recurrence/progression.
5. Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
6. Patient must have a measurable lesion(s) as per the RANO-HGG criteria for primarily enhancing lesions or RANO-LGG criteria for primarily non-enhancing lesions. The lesion (s) must be visible on 2 or more axial slices and have perpendicular diameters of at least 10 × 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1.
Key Inclusion Criteria for Part 2 and 3:
1. Must be ≥18 years old at the time of signing the ICF.
2. Must agree to submit sufficient tumor tissue for retrospective biomarker and histological analyses. This requirement may be waived in rare circumstances with approval by the Sponsor.
3. Has adequate hematologic and organ function
Key Inclusion Criteria for Part 2:
1. Diagnosis of histologically confirmed IDH1-mutant Grade 2, Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.
2. Have an IDH1 mutation (R132H/C/G/S/L) based on IHC (R132H only), polymerase chain reaction (PCR), or next-generation sequencing (NGS). CDKN2A/B status and at least 1 of the following must be confirmed: absence of 1p19q co-deletion by fluorescence in situ hybridization, array comparative genomic hybridization, or NGS; presence of an ATRX loss of function mutation by NGS; or loss of normal ATRX expression by IHC. A validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory must be used for all of the aforementioned results. Documentation of biomarker status, including redacted molecular pathology and NGS reports, must be provided during Screening.
3. Must not have experienced tumor recurrence or progression between first day of radiotherapy and randomization by local assessment per RANO 2.0.
4. Participants must have completed radiation therapy with a minimum of 80% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant . Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide.
Key Inclusion Criteria for Part 3:
1. Have had 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 and no longer than 5 years before the date of enrollment, 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.
2. Have histologically confirmed Grade 3 IDH-mutant oligodendroglioma according to WHO 2021 criteria per local assessment.
3. Have residual or recurrent measurable disease per RANO 2.0 and confirmed by BICR, at the time of enrollment.
4. Have an IDH1 mutation (R132H/C/G/S/L). The presence of 1p19q co-deletion must also be confirmed. All results must be generated using a validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory.
Key Exclusion Criteria for Part 1:
1. Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
2. Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
3. Surgery: within 3 weeks
4. Radiation therapy: within 12 weeks
5. Investigational agents: within 5 half-lives for other investigational agents
6. Patient did receive the prior therapy targeted to IDH1 mutation..
7. Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.
Key Exclusion Criteria for Part 2 and 3:
1. Participants with prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.
2. Have brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension.
3. Significant functional or neurocognitive deficits, including uncontrolled seizures, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
4. Evidence of diffuse leptomeningeal disease.
5. History of significant cardiac disease within 12 months prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
6. If taking corticosteroids, must be on a stable or decreasing dose for the 14 days prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
7. Participants with other malignancies must have received curative treatment and been disease-free for at least 3 years. Curatively resected skin cancer or curatively treated carcinoma in situ is allowed.
8. Have a condition that would interfere with, or increase the risk of, study participation.
Key Exclusion Criteria for Part 2 1. Participants may not have received any anticancer treatments other than surgery, radiation, concurrent/adjuvant temozolomide, and tumor-treating fields. Tumor-treating fields must be discontinued prior to randomization.
Key Exclusion Criteria for Part 3:
1\. Participants may not have received any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including radiotherapy.
Conditions
Glioma
Astrocytoma, Grade IV
IDH1-mutant Glioma
Astrocytoma, IDH-Mutant, Grade 3
Astrocytoma, IDH-Mutant, Grade 4
Astrocytoma, IDH-Mutant, Grade 2
Oligodendroglioma
Oligodendroglioma, IDH-Mutant and 1p/19q-Codeleted
Locations
- University of Alabama — Birmingham, Alabama, United States
- Mayo Clinic - Arizona — Phoenix, Arizona, United States
- St. Joseph's Hospital and Medical Center — Phoenix, Arizona, United States
- University of California San Diego — La Jolla, California, United States
- University of California, Los Angeles — Los Angeles, California, United States
- Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States
- Stanford University — Palo Alto, California, United States
- University of California — San Francisco, California, United States
- University of Colorado Health Cancer Care — Aurora, Colorado, United States
- Yale University — New Haven, Connecticut, United States
- University of Florida Health — Gainesville, Florida, United States
- Mayo Clinic - Florida — Jacksonville, Florida, United States
- University of Miami Health — Miami, Florida, United States
- Orlando Health Cancer Institute — Orlando, Florida, United States
- Emory University — Atlanta, Georgia, United States
- University of Chicago — Chicago, Illinois, United States
- Indiana University — Indianapolis, Indiana, United States
- University of Kansas Medical Center — Kansas City, Kansas, United States
- University of Kentucky — Lexington, Kentucky, United States
- Massachusetts General Hospital — Boston, Massachusetts, United States
- Dana-Farber Cancer Institute — Boston, Massachusetts, United States
- Henry Ford Hospital — Detroit, Michigan, United States
- Mayo Clinic - Rochester — Rochester, Minnesota, United States
- Washington University — St Louis, Missouri, United States
- Billings Clinic — Billings, Montana, United States
- Rutgers Cancer Institute — New Brunswick, New Jersey, United States
- NYU Langone Health — New York, New York, United States
- Icahn School of Medicine at Mount Sinai — New York, New York, United States
- Columbia University Medical Center — New York, New York, United States
- Memorial Sloan Kettering Cancer Center — New York, New York, United States
- University of Rochester Medical Center — Rochester, New York, United States
- Duke Cancer Institute — Durham, North Carolina, United States
- Atrium Health Wake Forest Baptist Comprehensive Cancer Center — Winston-Salem, North Carolina, United States
- Cleveland Clinic — Cleveland, Ohio, United States
- Oregon Health Science University — Portland, Oregon, United States
- Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States
- UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
- Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States
- University of Texas Southwestern Medical Center — Dallas, Texas, United States
- MD Anderson Cancer Center — Houston, Texas, United States
- University of Texas Health Mays Cancer Center — San Antonio, Texas, 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
- Inova Schar Cancer Institute — Fairfax, Virginia, United States
- Fred Hutch Cancer Center — Seattle, Washington, United States
- University of Wisconsin Health — Madison, Wisconsin, United States
- St Vincents Hospital Sydney (Kinghorn) — Darlinghurst, New South Wales, Australia
- Royal North Shore Hospital — Saint Leonards, New South Wales, Australia
- Royal Brisbane and Women's Hospital — Herston, Queensland, Australia
- Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia
- The Alfred — Melbourne, Victoria, Australia
- Sir Charles Gairdner Hospital — Nedlands, Western Australia, Australia
- Beijing Tiantan Hospital, Capital Medical University — Beijing, Beijing Municipality, China
- Sanbo Brain Hospital, Capital Medical University — Beijing, Beijing Municipality, China
- Xuanwu Hospital, Capital Medical University — Beijing, Beijing Municipality, China
- Peking Union Medical College Hospital — Beijing, Beijing Municipality, China
- The First Affiliated Hospital of Fujian Medical University — Fuzhou, Fujian, China
- Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China
- Xiangya Hospital of Central South University — Changsha, Hunan, China
- Huashan Hospital Affiliated to Fudan University — Shanghai, Shanghai Municipality, China
- West China Hospital of Sichuan University — Chengdu, Sichuan, China
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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.
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