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

Sep 22, 2026

Rare cartilaginous tumors (chondrosarcomas) have limited treatment options, and isocitrate dehydrogenase 1/2 (mIDH1/2) mutations are present in many cases. This phase 1b/2 study evaluates olutasidenib, an mIDH1 inhibitor, in patients with locally advanced or metastatic mIDH1 chondrosarcoma (NCT03684811). Objective response rate guided the primary assessment, with adverse events and progression-free/overall survival as key secondary endpoints. Twenty-three patients received 150 mg twice daily; outcomes include disease control without dose-limiting toxicities and specific activity in conventional chondrosarcoma.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Study overview

Treatment and endpoints

Patient outcomes and subgroup results

Background on chondrosarcoma and treatment context

Baseline demographics and disease characteristics

Article [https://doi.org/10.1038/s41467-026-68716-6](https://doi.org/10.1038/s41467-026-68716-6) Olutasidenib in recurrent/relapsed locally advanced or metastatic IDH1-mutated chondrosarcoma: phase 1b/2 trial Received: 7 May 2025 | Accepted: 12 January 2026 | | --- | | | | Check for updates | Robin L. Jones 1 , Roman Groisberg2, Jean-Yves Blay 3, Howard Colman4, Macarena De La Fuente5, Patricia Roxburgh 6, Mwe Mwe Chao7, Hua Tian7, Florence Duffaud8, Rastislav Bahleda9 & Brian A. Van Tine 10 Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Isocitrate dehydrogenase 1/2 (mIDH1/2) mutations occur in 65% of chondrosarcomas. Here we report safety and efﬁcacyofolutasidenib, an mIDH1 inhibitor, evaluated in patients with locally advanced or metastatic mIDH1 chondrosarcoma (Clinicaltrials.gov identiﬁer: NCT03684811). The primary endpoint was objective response rate by tumor evaluation; secondary endpoints included adverse events, progression-free and overall survival. Patients received olutasidenib 150 mg twice daily. Twenty-three patients were enrolled; 16 were diagnosed with conventional chondrosarcoma (cCS). Median age was 57 (range, 30-71) years. In 21 response-evaluable patients, 11 (52%) had stable disease, 8 (38%) had progressive disease, and 2 (10%) were not evaluable. Median progression-free survival (mPFS) was 2.0 months (95% conﬁdence interval [95%CI]: 1.7, 4.7); median overall survival was 16.0 months (95%CI: 7.7, not reached). Among patients with cCS, 10(63%)had stable disease;6(38%)had progressive disease; mPFS was 3.5 months (95%CI: 1.7, 5.1). Median overall survival in cCS patients was 19.0 months (95% CI: 7.7, not reached). No doselimiting toxicities were reported during the study. Olutasidenib was well tolerated and conferred disease control in cCS. Study limitations include open-label design and low patient sample due to rarity of cCS. Chondrosarcoma is a rare malignant bone tumor characterized by the production of cartilage matrix by tumor cells1,2. Chondrosarcomas are the second most common form of bone tumor, accounting for over 20% of primary malignant bone tumors3. Conventional chondrosarcoma (cCS) is the most common subtype, developing centrally in the medullar cavity of bone1. Other rarer subtypes of chondrosarcoma include dedifferentiated, mesenchymal, and clear cell1,4–6. Treatment options for people with chondrosarcoma are very limited and have not demonstrated impactful efﬁcacy. Because conventional chemotherapy is ineffective and non-curative in treating cCS6,7, localized disease is managed with surgical resection1,6,7. Mesenchymal chondrosarcomas are relatively chemo-sensitive and are treated with Ewing sarcoma chemotherapy schedules; however, dedifferentiated chondrosarcomas may not be as responsive to chemotherapy. One study reported that adjuvant chemotherapy using a 1Royal Marsden Hospital/Institute of Cancer Research, London, UK. 2Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. 3Centre Léon Bérard, the Comprehensive Cancer Centre, Lyon, France. 4Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT, USA. 5Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA. 6University of Glasgow, School of Cancer Sciences, Glasgow, UK. 7Rigel Pharmaceuticals, Inc., South San Francisco, CA, USA. 8CLIP/CEPCM, Aix-Marseille University (AMU), Marseille, France. 9Drug Development Department, Gustave Roussy Cancer Campus, Villejuif, France. 10Siteman Cancer Center, Washington University in Saint Louis, St. Louis, MO, USA. e-mail: [robin.jones4@nhs.net](robin.jones4@nhs.net) Table 1 | Patient demographics and disease characteristics at baseline | Characteristic | Conventional chondrosarcoma (n =16) | Non-conventional chondrosarcoma (dedifferentiated, n =5;
myxoid, n =1; unknown subtype, n =1) | All
patients
(N =23) | | --- | --- | --- | --- | | Sex, n (%) | | | | | Female | 6 (38) | 0 (0) | 6 (26

FAQs

What drug and molecular target does the phase 1b/2 trial evaluate?

The trial evaluates olutasidenib, an mIDH1 inhibitor, targeting mIDH1-mutated chondrosarcoma.

How was safety assessed, and were dose-limiting toxicities reported?

Safety was evaluated through adverse events, and no dose-limiting toxicities were reported during the study.

What were the main efficacy outcomes reported in the study?

The primary endpoint was objective response rate, and secondary endpoints included progression-free and overall survival; median progression-free survival was 2.0 months overall, with disease control observed in conventional chondrosarcoma.

Sep 22, 2026

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