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Chondrosarcoma - Sarcoma of the Year

(P 128) ISOCITRATE DEHYDROGENASE 1 (IDH1) MUTATION TESTING IN THE PHASE 3 STUDY OF IVOSIDENIB VS PLACEBO IN IDH1-MUTANT CONVENTIONAL CHONDROSARCOMA (CHONQUER)

Objective: Conventional chondrosarcoma (cCS) accounts for 85-90% of all CS cases. Mutations in isocitrate dehydrogenase 1 (IDH1) have been reported in approximately 50% of patients (pts) with cCS. Ivosidenib, an inhibitor of mutant IDH1 (mIDH1), demonstrated activity in a phase 1 trial that included pts with cCS. CHONQUER (NCT06127407) is an ongoing, phase 3, double-blind, randomized, placebo-controlled study to investigate the efficacy and safety of ivosidenib in pts with locally advanced or metastatic mIDH1 cCS. The frequency of mIDH1 in the first group of screened pts is reported here.

Methods: Key eligibility criteria include a histopathological diagnosis of cCS (all grades), locally-advanced or metastatic disease not eligible for curative resection; received 0 or 1 prior systemic treatment regimen; RECIST v1.1 progression/recurrence of disease; and mIDH1 confirmed by central testing with the Ion Torrent™ Oncomine™ Dx Express Test. Eligible pts will be randomized to receive ivosidenib 500 mg once daily or placebo. The primary endpoint is progression-free survival.

Results: As of 17 June 2025, 105 pts had undergone mIDH1 central testing. 81 (77.1%) pts had an initial valid test result, of which 29 (35.8%) were positive for mIDH1 and 52 (64.2%) were IDH1 wildtype. 14 (58.3%) of the 24 pts with an initial invalid test underwent additional testing, of which 3 pts were positive for mIDH1 and 7 pts were IDH1 wildtype and 4 had repetitive invalid test result. Thus, 32/91 (35.2%) pts with a valid test result had a positive mIDH1 test result. Invalid test results were mainly due to insufficient DNA extraction from the sample which can be impacted by low cellularity or tissue amount, and improper fixation, decalcification or other tissue processing steps.

Conclusion: IDH1 testing has begun to identify pts with mIDH1 cCS for inclusion to CHONQUER. The frequency of mIDH1 in our cohort is lower than anticipated based on literature. Technical reasons, as well as a potential selection bias, may explain this discrepancy.