CTNI-53. A GLOBAL, RANDOMIZED, DOUBLE-BLINDED, PHASE 3 STUDY OF VORASIDENIB VERSUS PLACEBO IN PATIENTS WITH ADULT-TYPE DIFFUSE GLIOMA WITH AN IDH1/2 MUTATION (INDIGO): UPDATED EFFICACY RESULTS

Abstract INTRODUCTION The Phase 3 INDIGO study (NCT04164901) evaluated vorasidenib, an oral, brain-penetrant, dual inhibitor of mutated isocitrate dehydrogenase 1/2 (mIDH1/2), in patients with mIDH1/2 diffuse glioma. The primary endpoint of progression-free survival (PFS) per blinded independent review committee (BIRC), and key secondary endpoint of time to next intervention (TTNI), were met in the positive, preplanned second interim analysis (IA2). The study was unblinded in March 2023 following independent data monitoring committee recommendation. Here, we present results after an additional 6 months of follow-up between the database lock for IA2 (September 6, 2022) and study unblinding (March 7, 2023). METHODS Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (≥12 years; Karnofsky Performance Status ≥80; measurable non-enhancing disease; surgery as only prior treatment; no immediate need of chemoradiotherapy). Patients were randomized 1:1 to vorasidenib 40 mg or placebo daily in 28-day cycles. RESULTS Overall, 331 patients were randomized (median age: 40.0 years; oligodendroglioma: 172; astrocytoma: 159). As of March 7, 2023, 123/168 (73%) patients remained on vorasidenib and 72/163 (44%) remained on placebo. PFS per BIRC remained in favor of vorasidenib (HR, 0.35; 95% CI, 0.25–0.49), and was consistent with PFS per investigator assessment (HR, 0.34; 95% CI, 0.23–0.50). Median PFS per BIRC: vorasidenib, not estimable (NE; 95% CI, 22.1–NE); placebo, 11.4 months (95% CI, 11.1–13.9). TTNI also remained in favor of vorasidenib (HR, 0.25; 95% CI, 0.16–0.40). Median TTNI: vorasidenib, NE (95% CI, NE–NE); placebo, 20.1 months (95% CI, 17.5–27.1). No new safety signals emerged. CONCLUSIONS Vorasidenib is a targeted therapy for patients with predominantly non-enhancing mIDH1/2 diffuse glioma following surgical intervention, as shown in the INDIGO population. These additional 6 months of follow-up confirm the previously reported statistically significant and clinically meaningful improvements in PFS and TTNI with vorasidenib.

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Journal
Neuro-Oncology
Published
2024-11-01
DOI
https://doi.org/10.1093/neuonc/noae165.0420
Citations
7
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
3.07
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article

CTNI-53. A GLOBAL, RANDOMIZED, DOUBLE-BLINDED, PHASE 3 STUDY OF VORASIDENIB VERSUS PLACEBO IN PATIENTS WITH ADULT-TYPE DIFFUSE GLIOMA WITH AN IDH1/2 MUTATION (INDIGO): UPDATED EFFICACY RESULTS

Andreas Felix Hottinger, Shlomit Yust‐Katz, Warren Mason, Adriana E. Tron et al.
7 citations
Neuro-Oncology
Glioma Diagnosis and Treatment
3.07
article

CTNI-53. A GLOBAL, RANDOMIZED, DOUBLE-BLINDED, PHASE 3 STUDY OF VORASIDENIB VERSUS PLACEBO IN PATIENTS WITH ADULT-TYPE DIFFUSE GLIOMA WITH AN IDH1/2 MUTATION (INDIGO): UPDATED EFFICACY RESULTS

Andreas Felix Hottinger, Shlomit Yust‐Katz, Warren Mason, Adriana E. Tron, Lori Steelman, Martin J. van den Bent, Islam Hassan, Joe Sammy Mendez, Pierre Giglio, Ingo K. Mellinghoff, Patrick Y. Wen, Benjamin M. Ellingson, Deborah T. Blumenthal, Yoshie Umemura, Jennifer Clarke, François Ducray, Yoshiki Arakawa, Elizabeth A. Maher, Timothy F. Cloughesy, Mehdi Touat, Katherine B. Peters, Burt Nabors, Juan Manuel Sepúlveda-Sánchez, Wolfgang Wick, Riccardo Soffietti, Dan Zhao, James Perry, Macarena de la Fuente, Shuchi S. Pandya
article en
7 citations

Abstract

Abstract INTRODUCTION The Phase 3 INDIGO study (NCT04164901) evaluated vorasidenib, an oral, brain-penetrant, dual inhibitor of mutated isocitrate dehydrogenase 1/2 (mIDH1/2), in patients with mIDH1/2 diffuse glioma. The primary endpoint of progression-free survival (PFS) per blinded independent review committee (BIRC), and key secondary endpoint of time to next intervention (TTNI), were met in the positive, preplanned second interim analysis (IA2). The study was unblinded in March 2023 following independent data monitoring committee recommendation. Here, we present results after an additional 6 months of follow-up between the database lock for IA2 (September 6, 2022) and study unblinding (March 7, 2023). METHODS Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (≥12 years; Karnofsky Performance Status ≥80; measurable non-enhancing disease; surgery as only prior treatment; no immediate need of chemoradiotherapy). Patients were randomized 1:1 to vorasidenib 40 mg or placebo daily in 28-day cycles. RESULTS Overall, 331 patients were randomized (median age: 40.0 years; oligodendroglioma: 172; astrocytoma: 159). As of March 7, 2023, 123/168 (73%) patients remained on vorasidenib and 72/163 (44%) remained on placebo. PFS per BIRC remained in favor of vorasidenib (HR, 0.35; 95% CI, 0.25–0.49), and was consistent with PFS per investigator assessment (HR, 0.34; 95% CI, 0.23–0.50). Median PFS per BIRC: vorasidenib, not estimable (NE; 95% CI, 22.1–NE); placebo, 11.4 months (95% CI, 11.1–13.9). TTNI also remained in favor of vorasidenib (HR, 0.25; 95% CI, 0.16–0.40). Median TTNI: vorasidenib, NE (95% CI, NE–NE); placebo, 20.1 months (95% CI, 17.5–27.1). No new safety signals emerged. CONCLUSIONS Vorasidenib is a targeted therapy for patients with predominantly non-enhancing mIDH1/2 diffuse glioma following surgical intervention, as shown in the INDIGO population. These additional 6 months of follow-up confirm the previously reported statistically significant and clinically meaningful improvements in PFS and TTNI with vorasidenib.

Neuro-OncologyVol. 26(Supplement_8)
Sunnybrook Health Science Centre (CA), Memorial Sloan Kettering Cancer Center (US), University of Miami (US), University of California, Los Angeles (US), Tel Aviv University (IL), University of California, San Francisco (US), University of Toronto (CA), Kyoto University (JP), University of Utah (US), Heidelberg University (DE), University of Michigan (US), Rabin Medical Center (IL), Huntsman Cancer Institute (US), Toronto General Hospital (CA), Erasmus MC (NL), University Hospital Heidelberg (DE), Centre Hospitalier Universitaire Vaudois (CH), Health Sciences Centre (CA), The Ohio State University Wexner Medical Center (US), University of Alabama at Birmingham (US), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Hospital Universitario 12 De Octubre (ES), Hôpital Pierre Wertheimer (FR), Dana-Farber Cancer Institute (US), Michigan Center for Translational Pathology (US), Pitié-Salpêtrière Hospital (FR), Centre de Recherche en Cancérologie de Lyon (FR), Duke Medical Center (US), Servier (France) (FR), Sylvester Comprehensive Cancer Center (US), University of Turin (IT), The University of Texas Southwestern Medical Center (US), Erasmus University Rotterdam (NL)
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Glioma Diagnosis and Treatment
3.07
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