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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
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.
Eligibility Criteria
Inclusion Criteria
- 1Have 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.
- 2Have 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.
- 3Have received 0 or 1 prior systemic treatment regimen in the advanced/metastatic setting for chondrosarcoma.
- 4Have radiographic progression/recurrence of disease according to RECIST v1.1 defined as:
- 5Radiographic 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.
- 6OR
- 7Any recurrence of disease (local and/or distant) after complete surgical resection and documented by imaging within 6 months (±2 weeks) before randomization.
- 8Have 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)
- 9Have 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
- 1Are unable to swallow oral medication.
- 2Pregnant or lactating women.
- 3Are participating in another interventional study at the same time; participation in noninterventional registries or epidemiological studies is allowed.
- 4Have received prior therapy with an IDH1 inhibitor
- 5Have received systemic anticancer therapy \<2 weeks prior to randomization (for investigational or immune-based anticancer therapy \<4 weeks).
- 6Have received radiotherapy \<2 weeks prior to randomization.
- 7Have 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.
- 8Have 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.
- 9Have had major surgery within 4 weeks prior to randomization.
- 10Have 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.
- 11Have LVEF \<40% by ECHO scan (or by other methods according to institutional practice) obtained within 28 days prior to randomization.
- 12Have 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.
- 13Have known medical history of progressive multifocal leukoencephalopathy (PML).
Locations
114 sites participating in this study
Emory Winship Cancer Institute
Atlanta, Georgia 30308
William Read
Usc Norris Comprehensive Cancer Center
Los Angeles, California 90033
Sarcoma Oncology Research Center
Santa Monica, California 90403
Victoria Chua-Alcala, MD