A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled Study of Ivosidenib in Participants ≥18 Years of Age With Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen
Summary
Study CL3-95031-007 (CHONQUER) is a Phase 3, international, multicenter, double-blind, randomized, placebo-controlled study of orally administered ivosidenib. Participants are required to have a histopathological diagnosis consistent with isocitrate dehydrogenase-1 (IDH1) gene-mutated, locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection. IDH1 mutant status will be determined during pre-screening/screening phase. Participant must have radiographic progression/recurrence of disease according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and have received 0 to 1 prior systemic treatment regimen in the advanced/metastatic setting for conventional chondrosarcoma. The primary endpoint is progression-free survival (PFS) in Grades 1 and 2 participants. Key secondary endpoints are PFS in all randomized participants, overall survival (OS) in Grades 1 and 2 participants, and OS in all randomized participants. Participants who meet enrollment criteria will be randomized 1:1 to receive oral ivosidenib 500mg once daily, or a matching placebo once daily.
Arms & interventions
- DrugIvosidenib 500mg
Provided as tablets, taken orally as two 250mg tablets once daily.
- DrugPlacebo
Provided as tablets, taken orally once daily.
Outcome measures
Primary
Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants
From randomization until BICR confirmed progressive disease or death due to any cause, whichever occurs first
Time frame: Up to approximately 31 months
Secondary
PFS based on BICR assessment in all randomized participants
Time frame: Up to approximately 31 months
Overall survival (OS) in Grade 1 and Grade 2 participants
Time frame: Up to 5 years
OS in all randomized participants
Time frame: Up to 5 years
PFS based on Investigator assessment in Grade 1 and Grade 2 participants
Time frame: Up to approximately 31 months
PFS based on Investigator assessment in all randomized participants
Time frame: Up to approximately 31 months
Objective response (OR) (confirmed complete response(CR) or confirmed partial response (PR)) of anti-tumor activity (using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1) in Grade 1 and Grade 2 participants
Time frame: Up to approximately 31 months
OR (confirmed CR or confirmed PR) of anti-tumor activity (using RECIST v1.1) in all randomized participants
Time frame: Up to approximately 31 months
Duration of response (DOR) in Grade 1 and Grade 2 participants
Time frame: Up to approximately 31 months
DOR in all randomized participants
Time frame: Up to approximately 31 months
Time to response (TTR) in Grade 1 and Grade 2 participants
Time frame: Up to approximately 31 months
TTR in all randomized participants
Time frame: Up to approximately 31 months
Disease control (DC) confirmed CR, confirmed PR, or stable disease (SD)) in Grade 1 and Grade 2 participants
Time frame: Through the end of the study (a maximum of 5 years after the study start)
DC (confirmed CR, confirmed PR, or SD) in all randomized participants
Time frame: Through the end of the study (a maximum of 5 years after the study start)
Duration of disease control (DoDC) in Grade 1 and Grade 2 participants
Time frame: Through the end of the study (a maximum of 5 years after the study start)
DoDC in all randomized participants
Time frame: Through the end of the study (a maximum of 5 years after the study start)
Number of Adverse Events (AEs)
Time frame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Number of Serious Adverse Events (SAEs)
Time frame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Number of Adverse Events of Special Interest (AESIs)
Time frame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Number of Adverse Events (AEs) leading to discontinuation, treatment interruption, and dose reduction
Time frame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) score
Time frame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) score
Time frame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Patient-Reported Outcomes Measurement Information System (PROMIS) score
Time frame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Ivosidenib concentration in plasma
Time frame: Through the end of the study (a maximum of 5 years after the study start)
2-hydroxyglutarate (2-HG) concentration in plasma
Time frame: Through the end of the study (a maximum of 5 years after the study start)
Eligibility criteria
Study locations (22)
Usc Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Sarcoma Oncology Research Center
Santa Monica, California, 90403
University of Colorado Cancer Center
Aurora, Colorado, 80045
Yale Cancer Center
New Haven, Connecticut, 06511
Mayo Clinic - Jacksonville, Fl
Jacksonville, Florida, 32224
University of Miami
Miami, Florida, 33136-1002
Emory Winship Cancer Institute
Atlanta, Georgia, 30308
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611-5975
University of Iowa Hospitals & Clinics- Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Johns Hopkins University
Baltimore, Maryland, 21287
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic - Rochester, Mn
Rochester, Minnesota, 55905
The Washington University
St Louis, Missouri, 63110
Nebraska Methodist Hospital
Omaha, Nebraska, 68118
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Duke University
Durham, North Carolina, 27710
Cleveland Clinic
Cleveland, Ohio, 44195
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Oregon Health & Science University Knight Cancer Institute
Portland, Oregon, 97239
University of Pittsburgh Medical Center-Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
The Univeristy of Texas Md Anderson Cancer Center
Houston, Texas, 77030
References
- Tap WD, Cote GM, Burris H, Gore L, Elias A, Beeram M, Conley AP, Gianolio DA, Qu Z, Pandya S, Trent JC. Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Long-term Safety and Clinical Activity in Patients with Conventional Chondrosarcoma. Clin Cancer Res. 2025 Jun 3;31(11):2108-2114. doi: 10.1158/1078-0432.CCR-24-4128.(PubMed)