Olutasidenib in recurrent/relapsed locally advanced or metastatic IDH1-mutated chondrosarcoma: phase 1b/2 trial

Key findings from this study

• The study found that olutasidenib achieved stable disease in 52% of response-evaluable patients with IDH1-mutated chondrosarcoma, with no dose-limiting toxicities reported.
• The authors report that conventional chondrosarcoma patients experienced a median progression-free survival of 3.5 months and median overall survival of 19.0 months.
• The researchers demonstrate that disease control was more pronounced in conventional chondrosarcoma (63% stable disease) compared to the overall cohort.

Overview

Olutasidenib, an isocitrate dehydrogenase 1 (IDH1) inhibitor, was evaluated for safety and efficacy in patients with recurrent or relapsed locally advanced or metastatic IDH1-mutated chondrosarcoma. The trial enrolled 23 patients, of whom 16 had conventional chondrosarcoma. This phase 1b/2 study addressed a disease with limited treatment options and high frequency of IDH1/2 mutations (65% prevalence).

Methods and approach

Patients received olutasidenib 150 mg twice daily. Primary endpoint was objective response rate assessed by tumor evaluation. Secondary endpoints included adverse events, progression-free survival, and overall survival. Twenty-one patients were response-evaluable. The open-label design and small sample size reflected the rarity of conventional chondrosarcoma.

Results

Among 21 response-evaluable patients, 11 (52%) achieved stable disease, 8 (38%) progressed, and 2 (10%) were not evaluable. Median progression-free survival was 2.0 months (95% CI: 1.7, 4.7 months). Median overall survival reached 16.0 months (95% CI: 7.7, not reached). In the conventional chondrosarcoma subset (n=16), 10 patients (63%) demonstrated stable disease while 6 (38%) progressed. Median progression-free survival in conventional chondrosarcoma was 3.5 months (95% CI: 1.7, 5.1 months), and median overall survival was 19.0 months (95% CI: 7.7, not reached). No dose-limiting toxicities emerged during the trial, and olutasidenib demonstrated acceptable tolerability across the cohort.

Implications

Olutasidenib conferred meaningful disease control in IDH1-mutated chondrosarcoma, particularly within the conventional histological subtype. The achievement of stable disease in a substantial proportion of patients suggests potential clinical benefit in a disease with otherwise limited therapeutic options. However, the modest objective response rates and relatively short median progression-free survival indicate that single-agent IDH1 inhibition may have limited capacity to induce tumor regression in this population. Future investigation might explore combination approaches or patient selection strategies based on molecular or clinical characteristics to optimize treatment outcomes.

Scope and limitations

This summary is based on the study abstract and available metadata. It does not include a full analysis of the complete paper, supplementary materials, or underlying datasets unless explicitly stated. Findings should be interpreted in the context of the original publication.