Phase 3 study of ivosidenib vs placebo in locally advanced or metastatic IDH1-mutant conventional chondrosarcoma untreated or previously treated with 1 systemic treatment regimen (CHONQUER).
Authors: Andrew J. Wagner, Silvia Stacchiotti, Channa Debruyne, Abdulazeez Salawu, Jean-Yves Blay, Fernando Augusto Batista Campos, Hiroaki Hiraga, Antoine Italiano, Akira Kawai, Ganessan Kichenadasse, Yoshihiro Nishida, Seth Pollack, Zhe Qu, Evinaa Sellaiah, Ilona Tala, Gabriel Tinoco, Jonathan C. Trent, Karina Costa Maia Vianna, Kan Yonemori, William D. Tap
Journal: Journal of Clinical Oncology (2025)

TPS11582 Background: Conventional chondrosarcoma (CS) is the most common chondrosarcoma subtype, accounting for 85% to 90% of all chondrosarcoma cases. A meta-analysis of 466 patients with CS reported the detection of IDH1/2 mutations in 51.2% of patients (38.7% IDH1 and 12.1% IDH2 mutations, mutually exclusive except for one case). In a phase 1 study (NCT02073994), the long term follow-up with a data cut-off date of 15 September 2022, showed that patients with advanced conventional CS (N = 13) who were treated with the IDH1 inhibitor ivosidenib had a median progression-free survival (PFS) of 7.4 months, a 6-month PFS rate of 53.8%, and an overall response rate (ORR) of 23.1% including 2 partial responses and 1 complete response. Ivosidenib demonstrated manageable toxicity with mostly grade 1 or 2 treatment emergent adverse events (AEs) (Tap et al. J Clin Oncol. 2023;41:11532). The current phase 3 CHONQUER study was designed to assess the efficacy and safety of ivosidenib treatment in patients with grades 1, 2 and 3 conventional CS. Methods: The CHONQUER study (NCT06127407) is a phase 3, international, multicenter, double-blind, randomized, placebo-controlled study of ivosidenib for patients with locally advanced or metastatic IDH1 mutant conventional CS untreated or previously treated with 1 systemic treatment regimen. Key eligibility criteria include a histopathological diagnosis of conventional CS (grades 1, 2, or 3), locally-advanced or metastatic setting not eligible for curative resection; ECOG PS 0-1; measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1); received 0 or 1 prior systemic treatment regimen in the advanced/metastatic setting for CS; radiographic progression/recurrence of disease over a period of 6 months according to RECIST v1.1 and IDH1 gene-mutated disease confirmed by central laboratory testing with the Ion Torrent Oncomine Dx Express Test. A total of 136 patients are planned to be enrolled and will be randomized 1:1 to ivosidenib or a matched placebo control. Randomization will be stratified by disease grade (grade 1 versus 2 versus 3) and locally advanced versus metastatic disease. The primary endpoint is PFS confirmed by Blinded Independent Central Review (BIRC) in grade 1 and 2 patients. The key secondary endpoints include PFS based on BIRC for all randomized patients, overall survival (OS) (both grade 1 and 2 and all randomized patients). Other secondary endpoints include PFS by investigator, overall response, duration of response, time to response, disease control, duration of disease control, adverse events, and health-related quality of life. 92 sites from 12 countries are planned to participate, including North and South America, Europe and Asian countries. Clinical trial information: NCT06127407 .