GliomaPhase 3SIGMANCT05303519
SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)
A Phase 3 study testing safusidenib in people with Glioma and Astrocytoma, Grade IV, run by Nuvation Bio Inc. at 61 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma, Astrocytoma, Grade IV, IDH1-mutant Glioma
- What is being tested?
- safusidenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 365 participants
- Where
- 61 sitesin 3 countries
- Study dates
- 5 Jun 2023to 1 Dec 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Have residual or recurrent measurable disease per RANO 2.0 and confirmed by BICR, at the time of enrollment.
- 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.
Who cannot join
- 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..
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- 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.
- 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.
- 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.
Trial locations and contacts
61 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
61 sites in 3 countries
United States46 sites, 46 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
Kerry Dycus, 404-778-1900, kerry.dycus@emory.edu
Byram Ozer, MD
- Recruiting
University of Colorado Health Cancer Care
Aurora, Colorado, 80045
Stephanie Biller, 720-848-2080, stephanie.biller@cuanschutz.edu
Denise Damek, MD
- Recruiting
Billings Clinic
Billings, Montana, 59101
Department of Neurology and Oncology Cancer Research, 406-435-7480, cancerresearch@billingsclinic.org
Matthew Smith-Cohn, MD
- Recruiting
University of Alabama
Birmingham, Alabama, 35294
Shirley Gibbs, 205-975-0447, sgibbs@uabmc.edu
Luis Nabors, MD
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02214
Julie Miller, 866-493-1612, julie.miller@mgh.harvard.edu
Julie Miller, M.D.
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Amanda Dresser, 877-338-7425, amanda_dresser@dfci.harvard.edu
David Reardon, MD
- Recruiting
UVA Health, Emily Couric Clinical Cancer Cente
Charlottesville, Virginia, 22903
CJ Woodburn, 434-243-9900, cjw4v@virginia.edu
David Schiff, M.D.
- Not yet recruiting
University of Chicago
Chicago, Illinois, 60637
Lauren Singer, 773-702-1000, cancerclinicaltrials@bsd.uchicago.edu
Lauren Singer, MD
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44106
Marci Ciolfi, 216-445-3307, ciolfim@ccf.org
Mina Lobbous, M.D.
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Omar Raslan, 214-645-2616, omar.raslan@utsouthwestern.edu
Michael Youssef, MD
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
Phillip Alther, 313-651-1606, palther1@hfhs.org
Tobias Walbert, MD
- Recruiting
Duke Cancer Institute
Durham, North Carolina, 27710
Erin Severance, (919) 668-6230, erin.k.bell@duke.edu
Katy Peters, M.D.
- Recruiting
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Stephanie Van Bebber, 571-472-4724, stephanie.vanbebber@inova.org
Adam Cohen, MD
- Recruiting
University of Florida Health
Gainesville, Florida, 32608
Victoria Hope, 352-273-9000, victoria.hope@neurosurgery@ufl.edu
Ashley Ghiaseddin, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Eva Gachimova, 713-792-2883, egachimova@mdanderson.org
Vinay Puduvalli, MD
- Recruiting
Indiana University
Indianapolis, Indiana, 46202
Jennifer Terrell, 317-278-6266, jkramey@iu.edu
Kathryn Nevel, MD
- Recruiting
Mayo Clinic - Florida
Jacksonville, Florida, 32224
Cancer Center Clinical Trials Referral Office, 1 855-776-0015, mcccprepteam@mayo.edu
Wendy Sherman, MD
- Recruiting
University of Kansas Medical Center
Kansas City, Kansas, 66160
Clinical Trial Nurse Navigator, 913-945-7552, CTNurseNav@kumc.edu
Tolga Tuncer, MD
- Recruiting
University of California San Diego
La Jolla, California, 92093
Sheila Medina-Torne, 858-246-1093, s4medina@health.ucsd.edu
David Piccioni, MD
- Recruiting
University of Kentucky
Lexington, Kentucky, 40536
Emilee Shape, 859-562-2128, emilee.shape@uky.edu
Villano, MD
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90095
Quan Li, 310-206-6909, quanli@mednet.ucla.edu
310-206-6909
- Recruiting
University of Wisconsin Health
Madison, Wisconsin, 53792
UW Cancer Connect, 800-622-8922, cancerconnect@uwhealth.org
Ankush Bhatia, MD
- Recruiting
University of Miami Health
Miami, Florida, 33136
Irene Marino, 305-243-2858, idm32@med.miami.edu
Macarena de la Fuente, MD
- Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37203
Vanderbilt-Ingram Cancer Center, 1-800-811-8480, cip@vumc.org
Ryan Merrell, MD
- Recruiting
Rutgers Cancer Institute
New Brunswick, New Jersey, 08901
Simbiat Ajao, 732-235-7503, ajao@cinj.rutgers.edu
Morana Vojnic, MD
- Recruiting
Yale University
New Haven, Connecticut, 06510
Amy Rodrigues, 203-737-7084, amy.rodrigues@yale.edu
Nicholas Blondin, MD
- Recruiting
NYU Langone Health
New York, New York, 10016
Olga Garduno-Ortega, 212-731-6267, olga.garduno-ortega@nyulangone.org
Jose McFaline-Figueroa, MD
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Camila Tanlam, 646-315-3698, camila.tanlam@mountsinai.org
Suzette Dayes-Mays, 646-531-4350, suzette.dayes-mays@mountsinai.org
- Recruiting
Columbia University Medical Center
New York, New York, 10032
Research Nurse Navigator, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Fabio Iwamoto, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Nancy Keith, 212 610 0538, keithn@mskcc.org
Kerina Yang, 901-883-0840, yangk3@mskcc.org
- Recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Jason Ledesma, 949-764-2794, jason.ledesma@hoag.org
Simon Khagi, MD
- Recruiting
Orlando Health Cancer Institute
Orlando, Florida, 32806
Janice Porter, 321-841-7246, janice.porter@orlandohealth.com
Alfredo Voloschin, MD
- Recruiting
Stanford University
Palo Alto, California, 94304
Sahara Rout, 650-723-4467, ssrout@stanford.edu
Seema Nagpal, MD
- Recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Community Research Operations & Enrollment (CROE), 251-600-9151, onctrialnow@jefferson.edu
Iyad Alnahhas, MD
- Recruiting
Mayo Clinic - Arizona
Phoenix, Arizona, 85013
Cancer Center Clinical Trials Referral Office, 1 855-776-0015, mcccprepteam@mayo.edu
Shannon Fortin Ensign, MD
- Recruiting
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Sandra Arenas, 602-406-3823, sandra.arenas@commonspirit.org
Yoshie Umemura, MD
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Linda Elias, 412-623-6037, eliaslj@upmc.edu
Michal Nisnboym Ziv, MD
- Recruiting
Oregon Health Science University
Portland, Oregon, 97239
Emily Pulliam, 503-494-0436, nsgclinicalresearch@ohsu.edu
Huan Vo, MD
- Recruiting
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Cancer Center Clinical Trials Referral Office, 1 855-776-0015, mcccprepteam@mayo.edu
Eva Galanis, MD
- Recruiting
University of Rochester Medical Center
Rochester, New York, 14642
Nimish Mohile, MD, 585-275-4401, nimish_mohile@urmc.rochester.edu
Nimish Mohile, MD
- Recruiting
Huntsman Cancer Insititute, University of Utah
Salt Lake City, Utah, 84112
Neuro Oncology Coordination, 801-585-0115, neurooncologycoordinationsstaff@hci.utah.edu
Howard Colman, MD
- Recruiting
University of Texas Health Mays Cancer Center
San Antonio, Texas, 78229
Leti Velten, 210-450-1921, velten@uthscsa.edu
Andrew Brenner, MD
- Recruiting
University of California
San Francisco, California, 94143
Neuro Onc New Patient Coordinator, 415-353-2193, neurooncnewpatientcoord@ucsf.edu
John De Groot, MD
- Recruiting
Fred Hutch Cancer Center
Seattle, Washington, 98195
Madhuri Poduri, 206-667-3691, mpoduri@fredhutch.org
Tyler Lanman, MD
- Recruiting
Washington University
St Louis, Missouri, 63110
Leslie Nehring, 314-830-8120, lnehring@wustl.edu
Omar Butt, MD
- Recruiting
Atrium Health Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
Morgan James, 336-713-6772, morgan.james@advocatehealth.org
Glenn Lesser, MD
China9 sites, 9 recruiting
- Recruiting
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100070
Xiaohui Ren, MD, 15011450618, xiaohuiren@aliyun.com
Xiaohui Ren, MD
- Recruiting
Sanbo Brain Hospital, Capital Medical University
Beijing, Beijing Municipality, 100093
Junping Zhang, MD, 13811099759, doczhjp@hotmail.com
Junping Zhang, MD
- Recruiting
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, 10053
Qingtang Lin, MD, 15801588169, linqingtang@xwhosp.org
Qingtang Lin, MD
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Wenbin Ma, MD, 13701364566, mawb@pumch.cn
Wenbin Ma, MD
- Recruiting
Xiangya Hospital of Central South University
Changsha, Hunan, 410008
Zhixiong Liu, MD, 13607318785, zhixiongliu@csu.edu.cn
Zhixiong Liu, MD
- Recruiting
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Yanhui Liu, MD, 18980601509, liuyh@scu.edu.com
Yanhui Liu, MD
- Recruiting
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350005
Dezhi Kang, MD, 0591-87982123, kdz99988@sina.com
Dezhi Kang, MD
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Zhongping Chen, MD, 020-87343310, chenzhp@sysucc.org.cn
Zhongping Chen, MD
- Recruiting
Huashan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 200040
Ying Mao, MD, 13801769152, my_gcp@sina.com
Ying Mao, MD
Australia6 sites, 6 recruiting
- Recruiting
St Vincents Hospital Sydney (Kinghorn)
Darlinghurst, New South Wales
Ashley Douglas, 02 9355 5613, ashley.douglas@svha.org.au
Subotheni Thavaneswaran, MD
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland
Amy Ives, 07 3646 7712, Amy.Ives@health.qld.gov.au
Zarnie Lwin, MD
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria
Clinical Trial Team (Monc A Team), (03) 8559 5000, PCCTU.MoncA@petermac.org
Jim Whittle, MD
- Recruiting
The Alfred
Melbourne, Victoria
Lucy Gately, MD, 03 9076 3129, l.gately@alfred.org.au
Lucy Gately, MD
- Not yet recruiting
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
Wee Chin, MD, 61 6457 3333, wee.chin@health.wa.gov.au
Wee Chin, MD
- Recruiting
Royal North Shore Hospital
Saint Leonards, New South Wales
Sally McCowatt, 02 9463 1181, sally.mccowatt@health.nsw.gov.au
Helen Wheeler, MD
About this study
Official title: A Phase 3, Multicenter, Clinical Study to Evaluate the Efficacy and Safety of Safusidenib Erbumine in Participants With Isocitrate Dehydrogenase 1 (IDH1)-Mutant Glioma
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.
Read the 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.
Part 1 was fully enrolled as of 19 Dec 2023 and participants are currently ongoing.
Part 2 will include approximately 300 participants with 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. 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.
Part 3 will include approximately 40 participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma with measurable disease who have undergone surgery as their only treatment and are not in need of immediate chemotherapy or radiotherapy. Participants will receive oral safusidenib 250 mg BID in 28-day continuous cycles until disease progression or another reason for discontinuation occurs.
- Conditions
- Glioma, Astrocytoma, Grade IV, IDH1-mutant Glioma, Astrocytoma, IDH-Mutant, Grade 3, Astrocytoma, IDH-Mutant, Grade 4, Astrocytoma, IDH-Mutant, Grade 2
- Being tested
- safusidenib, Placebo
- Keywords
- safusidenib, IDH1-mutant glioma, astrocytoma
- Medical subject headings
- Glioma, Glioblastoma, Astrocytoma, Lymphoma, Follicular, Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
safusidenibDrug
Also called DS-1001b, AB-218
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: safusidenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: 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
Measured: 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
Peak Plasma Concentration (Cmax)
Measured: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1: Tmax of safusidenib
the time for safusidenib to reach Cmax
Measured: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1: AUC8h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 8 hours
Measured: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1 : AUC12h of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 12 hours
Measured: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1: AUC24h [QD only] of safusidenib
Area under the plasma concentration curve (AUC) from time 0 to 24h hours for 500mg qd cohort
Measured: on Cycle 1 Day 1 and Day 8 (every cycle is 28 days)
Part 1 : Ctrough of safusidenib
Lowest plasma concentration reached after AB-218 administration
Measured: 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)
Part 1: Overall Response Rate (ORR) assessed by the investigator
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
Measured: from the first dose of study drug until the date of first documented disease progression, average 2 years
Part 1: Duration of Response (DOR) assessed by the Investigator
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
Measured: from the first dose of study drug until the date of first documented disease progression, average 2 years
Part 1: Disease control rate (DCR) assessed by the Investigator
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
Measured: from the first dose of study drug until the date of first documented disease progression, average 2 years
Part 1: Progression free survival (PFS) assessed by the Investigator
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
Measured: from the first dose of study drug until the date of first documented disease progression, average 2 years
Part1: Time to Response (TTR) assessed by the Investigator.
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.
Measured: From the first dose of study drug until the date of first documented objective response, average 2 years
Part 1: Overall Survival (OS)
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.
Measured: from the first dose of study drug to date of death, average 7 years
Part 2: Overall Survival (OS)
OS, defined as the time from randomization to death from any cause.
Measured: from randomization to date of death, average 7 years
Part 2: PFS assessed by the Investigator.
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.
Measured: from randomization until the date of first documented disease progression, average 2 years
Part2: Time to Next Intervention (TTNI) by Investigator assessment
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.
Measured: From randomization until the date of next treatment, average 2 years
Part2: DCR assessed by BICR and by the Investigator
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
Measured: from randomization until the date of first documented disease progression, average 2 years
Part2: ORR
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.
Measured: from randomization until the date of first documented disease progression, average 2 years
Part2: DOR, assessed by BICR and the Investigator
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.
Measured: from randomization until the date of first documented disease progression, average 2 years
Part2: Time to Response (TTR) assessed by BICR and by the Investigator
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.
Measured: From randomization until the date of first documented objective response, average 2 years
Part2: Health-related quality of life
The Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire
Measured: From the first dose of study drug to treatment discontinuation, average 2 years
Part2: Safety and tolerability
AEs graded by NCI CTCAE v5.0, laboratory abnormalities as graded by NCI CTCAE v5.0, vital signs, physical examinations, and ECGs.
Measured: from the first dose of study drug until 30 days after treatment discontinuation, average 2 years
Part2: Seizure Activity
Defined as seizure frequencies and severity including type of seizure, seizure-related AEs, and changes in anti-epileptic medications.
Measured: from the first dose of study drug until the date of first documented disease progression, average 2 years
Part2: Safusidenib PK Profile
Defined as safusidenib concentrations and PK parameters.
Measured: from the first dose of study drug through 20 weeks
Part 3: ORR, assessed by the Investigator
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 the Investigator.
Measured: From first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: DOR, assessed by BICR and the Investigator
DOR, 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 2.0, or death (by any cause in the absence of progression), as assessed by the BICR and the Investigator.
Measured: From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: Time to Next Intervention (TTNI)
TTNI, defined as the time from the first dose of study drug to initiation of the first subsequent anticancer therapy.
Measured: From the first dose of study drug until the date of next treatment, average 18 months
Part 3: PFS assessed by BICR and the Investigator.
PFS, defined as the time from the first dose of study drug 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 BICR and the Investigator.
Measured: From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: DCR assessed by BICR and by the Investigator
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
Measured: From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: Time to Response (TTR) assessed by BICR and by the Investigator
TTR, defined as the time from the first dose of study drug to the first documentation of objective response (CR, PR, or MR) per RANO 2.0, as assessed by the BICR and the Investigator.
Measured: From the first dose of study drug until the date of first documented disease progression, average 18 months
Part 3: Overall Survival (OS)
OS, defined as the time from the first dose of study drug to death from any cause.
Measured: From the first dose of study drug until the date of death, average 7 years
Part 3: Safety and tolerability
AEs graded by NCI CTCAE v5.0, laboratory abnormalities as graded by NCI CTCAE v5.0, vital signs, physical examinations, and ECGs.
Measured: From the first dose of study drug until 30 days after treatment discontinuation, average 18 months
Part 3: Safusidenib PK Profile
Defined as safusidenib concentrations and PK parameters.[Time Frame: from the first dose of study drug through 20 weeks]
Measured: From the first dose of study drug through 20 weeks
Part 3: Health-related quality of life
The Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Quality of Life in Epilepsy (QOLIE-10-P) questionnaires.
Measured: From the first dose of study drug to treatment discontinuation, average 18 months
Part 3: Seizure Activity
Defined as seizure frequencies and severity including type of seizure, seizure-related AEs, and changes in anti-epileptic medications.
Measured: From the first dose of study drug until the date of first documented disease progression, average 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start5 Jun 2023
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 365 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nuvation Bio Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AnHeart Therapeutics Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05303519
- Sponsor's protocol ID
- AB-218-G203
- Acronym
- SIGMA
- Status last verified
- Oct 2026
- First submitted
- 13 Mar 2022
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No