Clinical Summary: 

• Design/Population: Updated analysis from the phase 3 INDIGO trial evaluating vorasidenib, a dual mutant IDH1/IDH2 inhibitor, versus placebo in patients with grade 2 IDH-mutant gliomas, including astrocytomas and oligodendrogliomas.
• Key Outcomes: With nearly twice the follow-up of the initial report, vorasidenib continued to demonstrate durable disease control, prolonged progression-free survival, and increasing tumor shrinkage over time. Most patients remained on treatment or had not required additional therapy, while the safety profile remained consistent with prior analyses.
• Clinical Relevance: These long-term findings reinforce vorasidenib as an effective disease-modifying therapy for IDH-mutant grade 2 glioma and support its role in delaying disease progression and the need for subsequent treatment.

Timothy Cloughesy, MD, University of California, Los Angeles, California, discusses updated results from the phase 3 INDIGO trial evaluating vorasidenib in patients with grade 2 IDH-mutant gliomas. The original study demonstrated a significant progression-free survival benefit, leading to substantial interest in the use of targeted IDH inhibition for lower-grade gliomas.

With extended follow-up, the trial continues to show durable benefit, including sustained disease control, increasing rates of tumor shrinkage, and delayed need for subsequent therapies. No new safety concerns emerged, and treatment-related liver enzyme elevations remained stable over time, supporting the long-term tolerability of vorasidenib.

Dr  Cloughesy presented these results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

Hi, I'm Tim Cloughesy. I'm a neuro-oncologist at UCLA. The data being presented today are from the INDIGO trial, and this is an update to previously reported results.

INDIGO is a phase 3 randomized trial in patients with IDH-mutant grade 2 gliomas, including both astrocytomas and oligodendrogliomas. The study evaluated vorasidenib, a mutant IDH inhibitor. Vorasidenib inhibits both mutant IDH1 and mutant IDH2, which allows it to be used broadly across IDH-mutant gliomas.

This presentation provides an update on the trial, and one of the important points is that the original analysis demonstrated such a significant treatment effect—with a hazard ratio of approximately 0.4—that the initial follow-up was relatively limited, at about 20 months. Now we have nearly an additional 20 months of follow-up, giving us the opportunity to better understand the durability of benefit and the long-term impact of therapy. 

One important observation is that approximately 58% of patients remain on study treatment, which is very encouraging. We also now have a more mature estimate of median progression-free survival. At the initial analysis, median progression-free survival was around 27 months. Subsequently it became not estimable, and now with longer follow-up we estimate median progression-free survival to be approximately 44 months. That is generally in line with where we anticipated the data might ultimately mature.

Another important finding is that only about 28% of patients have gone on to receive subsequent therapy. In other words, roughly 72% of patients have not required additional treatment and either remain on study drug or continue to be monitored. I think another particularly interesting aspect is the effect on tumor size. We often focus on progression-free survival, but we also want to understand whether tumors are actually shrinking. As follow-up has extended from approximately 20 months to nearly 40 months, we have seen both the depth and breadth of tumor shrinkage continue to increase. Early on, the rate of objective responses, including minor and partial responses, was around 10%. Now that response rate has increased to approximately 20%, and it continues to rise over time. This suggests that we may not yet have reached the maximal treatment effect in terms of radiographic response.

We also have updated safety information. The overall safety profile remains very consistent with what has previously been reported. The primary adverse event of interest continues to be elevations in liver function tests. Importantly, the frequency of these events appears to have plateaued, and the incidence is essentially unchanged when comparing the earlier 20-month analysis with the current longer-term follow-up.

Overall, this is a very encouraging update. We are gaining a much better understanding of the durability of benefit with vorasidenib, how long patients may remain on treatment, and the continued impact on tumor control over time. We look forward to providing additional updates as follow-up continues and we learn more from the INDIGO study.

Source:

Cloughesy TF, van den Bent MJ, Blumenthal DT, et al. A global, randomized, double-blinded, phase 3 trial of vorasidenib vs placebo in patients with grade 2 glioma with an IDH1/2 mutation (INDIGO): Updated efficacy and safety. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 2010.