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

Area of Science:

• Oncology
• Medical Genetics

Background:

• Chondrosarcomas are rare bone cancers with few treatment options.
• Mutations in isocitrate dehydrogenase 1/2 (mIDH1/2) are found in 65% of chondrosarcomas, presenting a potential therapeutic target.

Purpose of the Study:

• To evaluate the safety and efficacy of olutasidenib, a specific mIDH1 inhibitor.
• To assess olutasidenib's impact on objective response rate, progression-free survival, and overall survival in patients with advanced mIDH1 chondrosarcoma.

Main Methods:

• A Phase I/II clinical trial (NCT03684811) enrolled patients with locally advanced or metastatic mIDH1 chondrosarcoma.
• Olutasidenib was administered at a dose of 150 mg twice daily.
• Tumor response, adverse events, progression-free survival, and overall survival were primary and secondary endpoints.

Main Results:

• Of 21 response-evaluable patients, 52% had stable disease and 38% had progressive disease.
• Median progression-free survival was 2.0 months, and median overall survival was 16.0 months.
• In the subgroup of 16 patients with conventional chondrosarcoma (cCS), 63% had stable disease, with a median progression-free survival of 3.5 months and median overall survival of 19.0 months.

Conclusions:

• Olutasidenib was well-tolerated and demonstrated disease control in patients with conventional chondrosarcoma.
• The study suggests olutasidenib may be a promising therapeutic option for mIDH1 chondrosarcoma, despite limitations including an open-label design and small sample size.