(P 87) SAFETY AND EFFICACY OF OLUTASIDENIB, AN IDH1 MUTANT INHIBITOR, FOR THE TREATMENT OF RECURRENT/ RELAPSED LOCALLY ADVANCED OR METASTATIC IDH1 MUTATED CHONDROSARCOMA

Objective: Chondrosarcomas (CS) are rare cartilaginous neoplasms with conventional CS (cCS) accounting for 90% of CS. Other variants consists of dedifferentiated, mesenchymal, and clear cell which all have distinct clinicopathologic features. Surgical excision is the mainstay of treatment. Chemotherapy is ineffective in cCS. Mutations in isocitrate dehydrogenase 1/2 (IDH1/2m+) occur in 65% of CS and are thought to contribute to tumorigenesis. Consequently, inhibition of IDH1/2 m+ represents an attractive therapeutic option. We report the safety and efficacy of olutasidenib (OLU), an IDH1m+ inhibitor approved for recurrent/relapsed (R/R) AML, in patients with CS.

Methods: This analysis includes patients with R/R, locally advanced or metastatic CS treated with OLU 150mg BID in a phase 1b/2 study evaluating OLU in IDH1m+ advanced solid tumors (NCT03684811).

Results: 23 patients were enrolled and 16 had cCS, 5 dedifferentiated and 1 each myxoid or unknown subtypes. Median age at consent was 57 years (yrs) (30-71) with a male preponderance (74%). Median number of prior regimens was 2 (1-5). Tumor grade (Gr) included 1 (4%) Gr1, 7 (30%) Gr2, 7 (30%) Gr3, and 8 (35%) unknown. At screening, 17 (74%) patients had metastatic disease while 2 (9%) had locally advanced disease, and 4 (17%) were unknown. 91% (21) patients experienced a treatment emergent adverse event (TEAE) with 48% (11) with serious. 3 (13%) discontinued OLU due to a TEAE. In 21 response-evaluable patients, 11 (52%) had stable disease (SD), 8 (38%) had progressive disease (PD), and 2 (10%) not evaluable. Overall median PFS (mPFS) was 2.71 months (mos) (95% CI: 1.71, 4.88). Subset analysis of the 16 cCS patients showed 10 (63%) SD and 6 (37%) PD. mPFS in this cohort was 3.55 mos (95% CI: 1.74, 5.10) and among the 10 with SD, mPFS was 4.88 mos (95% CI: 1.81, 10.5) with 6 and 12 mos PFS at 100% and 90%, respectively. Notably, following disease progression, 2 patients continued OLU for >2 yrs due to clinical benefit including resolution of CNS metastatic lesions in one.

Conclusion: OLU was well tolerated and conferred durable disease control in cCS. OLU may represent a treatment option for patients with IDH1m+ cCS who otherwise have no other effective treatment.