SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)

NCT05303519 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AB-218-G203
• Study Type: interventional
• Target: 365
• Locations: 3 countries
• Sites: 45

Brief Summary

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.

Conditions

Oligodendroglioma; Oligodendroglioma, IDH-Mutant and 1p/19q-Codeleted; Glioma; Astrocytoma, Grade IV; IDH1-mutant Glioma; Astrocytoma, IDH-Mutant, Grade 3; Astrocytoma, IDH-Mutant, Grade 4; Astrocytoma, IDH-Mutant, Grade 2

Keywords

safusidenib; IDH1-mutant glioma; astrocytoma

Outcome Measures

Primary Outcomes (3)

• 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

  From participants sign ICF to 30 days after last dose，average 2 years

• 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).

  From randomization until the date of first documented disease progression, average 2 years

• 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

  From the first dose of study drug until the date of first documented disease progression, average 18 months

Secondary Outcomes (34)

• Part 1: Cmax of safusidenib

  on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)

• Part 1: Tmax of safusidenib

  on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)

• Part 1: AUC8h of safusidenib

  on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)

• Part 1 : AUC12h of safusidenib

  on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)

• Part 1: AUC24h [QD only] of safusidenib

  on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)

Study Arms (8)

safusidenib 125mg bid (part 1)

EXPERIMENTAL

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.

Drug: safusidenib

safusidenib 250mg bid (part 1)

EXPERIMENTAL

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.

Drug: safusidenib

safusidenib 500mg qd (part 1)

EXPERIMENTAL

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.

Drug: safusidenib

safusidenib 375mg bid (part 1)

EXPERIMENTAL

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.

Drug: safusidenib

safusidenib 500mg bid (part 1)

EXPERIMENTAL

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.

Drug: safusidenib

safusidenib 250mg bid (Part 2)

EXPERIMENTAL

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.

Drug: safusidenib

placebo (Part 2)

PLACEBO COMPARATOR

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.

Drug: Placebo

safusidenib 250mg bid (Part 3)

EXPERIMENTAL

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.

Drug: safusidenib

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.

Also known as: DS-1001b, AB-218

safusidenib 125mg bid (part 1); safusidenib 250mg bid (Part 2); safusidenib 250mg bid (Part 3); safusidenib 250mg bid (part 1); safusidenib 375mg bid (part 1); safusidenib 500mg bid (part 1); safusidenib 500mg qd (part 1)

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.

placebo (Part 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
• 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.
• Must be ≥18 years old at the time of signing the ICF.
• 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.
• Has adequate hematologic and organ function
• 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.
• 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.
• Must not have experienced tumor recurrence or progression between first day of radiotherapy and randomization by local assessment per RANO 2.0.
• 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.
• 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.
• Have histologically confirmed Grade 3 IDH-mutant oligodendroglioma according to WHO 2021 criteria per local assessment.

You may not qualify if:

• Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
• 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
• Patient did receive the prior therapy targeted to IDH1 mutation..
• Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.
• 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.
• Have 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, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
• Evidence of diffuse leptomeningeal disease.
• History of significant cardiac disease within 12 months prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
• 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).
• 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.
• Have a condition that would interfere with, or increase the risk of, study participation.

Sponsors & Collaborators

• Nuvation Bio Inc.: lead
• AnHeart Therapeutics Inc.: collaborator

Study Sites (45)

University of Alabama

Birmingham, Alabama, 35294, United States

RECRUITING

Mayo Clinic - Arizona

Phoenix, Arizona, 85013, United States

RECRUITING

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

RECRUITING

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

University of California

San Francisco, California, 94143, United States

RECRUITING

University of Colorado Health Cancer Care

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

University of Florida Health

Gainesville, Florida, 32608, United States

RECRUITING

Mayo Clinic - Florida

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami Health

Miami, Florida, 33136, United States

RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27710, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44106, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Insititute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

UVA Health, Emily Couric Clinical Cancer Cente

Charlottesville, Virginia, 22903, United States

RECRUITING

Fred Hutch Cancer Center

Seattle, Washington, 98195, United States

RECRUITING

University of Wisconsin Health

Madison, Wisconsin, 53792, United States

RECRUITING

St Vincents Hospital Sydney (Kinghorn)

Darlinghurst, New South Wales, Australia

RECRUITING

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

NOT YET RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

RECRUITING

The Alfred

Melbourne, Victoria, Australia

RECRUITING

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

Sanbo Brain Hospital, Capital Medical University

Beijing, Beijing Municipality, 100093, China

RECRUITING

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 10053, China

RECRUITING

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

NOT YET RECRUITING

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350005, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, 410008, China

NOT YET RECRUITING

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma; Lymphoma, Follicular; Oligodendroglioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Clinical Trials at Nuvation Bio

CONTACT

332-208-6102; ClinicalTrials@nuvationbio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2022
• First Posted: March 31, 2022
• Study Start: June 5, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (31); AU (5); CN (9)