Abstract
1721MO Safety and efficacy of olutasidenib, an IDH1 mutant inhibitor, for the treatment of recurrent/relapsed or locally advanced or metastatic IDH1 mutated chondrosarcoma
Annals of oncology, Vol.35(Supplement 2), pp.S1031-S1032
09/2024
DOI: 10.1016/j.annonc.2024.08.1813
Abstract
Background
Chondrosarcomas (CS) are rare cartilaginous neoplasms with conventional CS (cCS) accounting for 90% of CS. Other variants consist 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 Ib/II 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.
Conclusions
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.
Details
- Title: Subtitle
- 1721MO Safety and efficacy of olutasidenib, an IDH1 mutant inhibitor, for the treatment of recurrent/relapsed or locally advanced or metastatic IDH1 mutated chondrosarcoma
- Creators
- R.L. Jones - Royal Marsden HospitalR. Groisberg - Rutgers Cancer InstituteJ-Y. Blay - Centre Léon BérardH. Colman - University of UtahM. de la Fuente - University of MiamiM. Milhem - University of IowaP. Roxburgh - University of GlasgowM.M. Chao - Rigel (United States)H. Tian - Rigel (United States)F. Duffaud - Hôpital de la TimoneC.P. Massard - DITEP Department, Gustave Roussy - Cancer Campus, Villejuif, FranceB.A. Van Tine - Washington University in St. Louis School of Medicine
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.35(Supplement 2), pp.S1031-S1032
- DOI
- 10.1016/j.annonc.2024.08.1813
- ISSN
- 0923-7534
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 09/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984704831302771
Metrics
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