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).

Abstract

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 .