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RecruitingInterventionalPhase 3

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

NCT ID: NCT06127407Sponsor: Servier Bio-Innovation LLCLast updated: 2026-02-06

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Have a histopathological diagnosis (fresh or banked tumor biopsy sample collected within the last 3 years) consistent with locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection. * Have at least one BICR-confirmed measurable lesion as defined by RECIST v1.1. Participants who have received prior radiation therapy are eligible provided measurable disease falls outside of the treatment field or within the field and has shown ≥20% growth in size since post-treatment assessment. * Have received 0 or 1 prior systemic treatment regimen in the advanced/metastatic setting for chondrosarcoma. * Have radiographic progression/recurrence of disease according to RECIST v1.1 defined as: 1. Radiographic progression of disease (local and/or distant) documented by 2 imaging assessments performed no more than 6 months (±2 weeks) apart within 12 months before randomization. OR 2. Any recurrence of disease (local and/or distant) after complete surgical resection and documented by imaging within 6 months (±2 weeks) before randomization. * Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available that was sourced from either a primary or metastatic tumor lesion) based on central laboratory testing (R132C/L/G/H/S mutation variants tested) * Have recovered from any clinically relevant sequelae and toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. Exclusion Criteria: * Are unable to swallow oral medication. * Pregnant or lactating women. * Are participating in another interventional study at the same time; participation in noninterventional registries or epidemiological studies is allowed. * Have received prior therapy with an IDH1 inhibitor * Have received systemic anticancer therapy \<2 weeks prior to randomization (for investigational or immune-based anticancer therapy \<4 weeks). * Have received radiotherapy \<2 weeks prior to randomization. * Have known symptomatic brain metastases requiring steroids \>10 mg per day prednisone (or equivalent). Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued or reduced corticosteroid treatment \<=10 mg per day for these metastases for at least 4 weeks and have radiographically stable disease of brain lesions for at least 3 months prior to randomization. * Have a history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated carcinoma in situ; or c) pT1-2 prostatic cancer Gleason score \<6 or d) participant is free of other primary solid or liquid tumor for ≥ 1 year prior to the start of study treatment and, in the opinion of the Investigator, the disease will not affect participant's outcome in the setting of current chondrosarcoma diagnosis. * Have had major surgery within 4 weeks prior to randomization. * Have significant active cardiac disease within 6 months prior to randomization, including New York Heart Association (NYHA) Class III or IV congestive heart failure; myocardial infarction; unstable angina; and/or stroke. * Have LVEF \<40% by ECHO scan (or by other methods according to institutional practice) obtained within 28 days prior to randomization. * Have a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome). Participants with a bundle branch block combined with a prolonged QTcF interval may be permitted based on local cardiology assessment. * Have known medical history of progressive multifocal leukoencephalopathy (PML).

Study locations (22)

Usc Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Recruiting

Sarcoma Oncology Research Center

Santa Monica, California, 90403

Recruiting
Victoria Chua-Alcala, MD · Contact

University of Colorado Cancer Center

Aurora, Colorado, 80045

Recruiting

Yale Cancer Center

New Haven, Connecticut, 06511

Recruiting
Sharon Huie · Contact

Mayo Clinic - Jacksonville, Fl

Jacksonville, Florida, 32224

Recruiting
Steven Attia, Dr · Contact

University of Miami

Miami, Florida, 33136-1002

Recruiting

Emory Winship Cancer Institute

Atlanta, Georgia, 30308

Recruiting
William Read · Contact

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611-5975

Recruiting

University of Iowa Hospitals & Clinics- Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242

Recruiting

Johns Hopkins University

Baltimore, Maryland, 21287

Recruiting

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
DFCI Sarcoma Center · Contact

Mayo Clinic - Rochester, Mn

Rochester, Minnesota, 55905

Recruiting

The Washington University

St Louis, Missouri, 63110

Recruiting

Nebraska Methodist Hospital

Omaha, Nebraska, 68118

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
William Tap, MD · Principal Investigator

Duke University

Durham, North Carolina, 27710

Recruiting
Richard Riedel, MD · Contact

Cleveland Clinic

Cleveland, Ohio, 44195

Recruiting

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

Recruiting
Luiza Stoeva · Contact

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, 97239

Recruiting
OHSU Clinical Trials Office · Contact

University of Pittsburgh Medical Center-Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Recruiting

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

Recruiting
Clinical Research Coordinator · Contact

The Univeristy of Texas Md Anderson Cancer Center

Houston, Texas, 77030

Recruiting

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)