NCT05303519: SIGMA

SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)

Recruiting now Phase 3 Last updated 5 March 2026

What this trial tests

Phase 3 trial testing safusidenib in Glioma in 365 participants. Currently enrolling.

Timeline

5 June 2023

Primary endpoint
1 December 2028

1 December 2030

Quick facts

Lead sponsor	Nuvation Bio Inc.
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	365
Start date	5 June 2023
Primary completion	1 December 2028
Estimated completion	1 December 2030
Sites	45 locations across China, United States, Australia

Drugs / interventions tested

• safusidenib — full drug profile →
• Placebo

Conditions studied

• Glioma — all drugs for Glioma →
• Astrocytoma, Grade IV — all drugs for Astrocytoma, Grade IV →
• IDH1-mutant Glioma — all drugs for IDH1-mutant Glioma →
• Astrocytoma, IDH-Mutant, Grade 3 — all drugs for Astrocytoma, IDH-Mutant, Grade 3 →

Sponsor

Nuvation Bio Inc. — full company profile →

Who can join

18 and older, any sex, with Glioma or Astrocytoma, Grade IV. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas.
   Natsume A, Arakawa Y, Narita Y, Sugiyama K, et al · · 2023 · cited 69× · PMID 35722822 · DOI 10.1093/neuonc/noac155
2. The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer.
   Liu Y, Xu W, Li M, Yang Y, et al · · 2023 · cited 22× · PMID 37139412 · DOI 10.1016/j.apsb.2022.12.019
3. The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.
   de la Fuente MI, Touat M, van den Bent MJ, Preusser M, et al · · 2025 · cited 16× · PMID 39723472 · DOI 10.1093/neuonc/noae259
4. Treatment of IDH-mutant glioma in the INDIGO era.
   Lin MD, Tsai AC, Abdullah KG, McBrayer SK, et al · · 2024 · cited 16× · PMID 39025958 · DOI 10.1038/s41698-024-00646-2
5. Immunotherapy Approaches in Isocitrate-Dehydrogenase-Mutant Low-Grade Glioma.
   Gallus M, Kwok D, Lakshmanachetty S, Yamamichi A, et al · · 2023 · cited 16× · PMID 37509387 · DOI 10.3390/cancers15143726
6. Oncometabolite 2-hydroxyglutarate regulates anti-tumor immunity.
   Cai M, Zhao J, Ding Q, Wei J. · · 2024 · cited 14× · PMID 38293535 · DOI 10.1016/j.heliyon.2024.e24454
7. State of the Art in Low-Grade Glioma Management: Insights From Isocitrate Dehydrogenase and Beyond.
   Schaff LR, Ioannou M, Geurts M, van den Bent MJ, et al · · 2024 · cited 13× · PMID 38723228 · DOI 10.1200/edbk_431450
8. IDH-mutant gliomas in children and adolescents - from biology to clinical trials.
   Evans L, Trinder S, Dodgshun A, Eisenstat DD, et al · · 2024 · cited 5× · PMID 39876890 · DOI 10.3389/fonc.2024.1515538