Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Ivosidenib 500mg
  Provided as tablets, taken orally as two 250mg tablets once daily.
• Препарат Placebo
  Provided as tablets, taken orally once daily.

Первичные конечные точки

• Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants [Срок оценки: Up to approximately 31 months]

Вторичные конечные точки (12)

• PFS based on BICR assessment in all randomized participants [Срок оценки: Up to approximately 31 months]
• Overall survival (OS) in Grade 1 and Grade 2 participants [Срок оценки: Up to 5 years]
• OS in all randomized participants [Срок оценки: Up to 5 years]
• PFS based on Investigator assessment in Grade 1 and Grade 2 participants [Срок оценки: Up to approximately 31 months]
• PFS based on Investigator assessment in all randomized participants [Срок оценки: 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 [Срок оценки: Up to approximately 31 months]
• OR (confirmed CR or confirmed PR) of anti-tumor activity (using RECIST v1.1) in all randomized participants [Срок оценки: Up to approximately 31 months]
• Duration of response (DOR) in Grade 1 and Grade 2 participants [Срок оценки: Up to approximately 31 months]
• DOR in all randomized participants [Срок оценки: Up to approximately 31 months]
• Time to response (TTR) in Grade 1 and Grade 2 participants [Срок оценки: Up to approximately 31 months]
• TTR in all randomized participants [Срок оценки: Up to approximately 31 months]
• Disease control (DC) confirmed CR, confirmed PR, or stable disease (SD)) in Grade 1 and Grade 2 participants [Срок оценки: Through the end of the study (a maximum of 5 years after the study start)]

Критерии участия

Критерии включения

• 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:

• 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

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 22 центра

• Usc Norris Comprehensive Cancer Center — Los Angeles
• Sarcoma Oncology Research Center — Santa Monica
• University of Colorado Cancer Center — Aurora
• Yale Cancer Center — New Haven
• Mayo Clinic - Jacksonville, Fl — Jacksonville
• University of Miami — Miami
• Emory Winship Cancer Institute — Atlanta
• Robert H. Lurie Comprehensive Cancer Center of Northwestern University — Chicago
• … и ещё 14 центров

Бразилия · 11 центров

• Liga Norte Riograndense Contra O Cancer — Natal
• Hospital de Amor - Barretos — Barretos
• Hospital Das Clínicas Da Ufmg — Belo Horizonte
• CIONC — Curitiba
• Cepon - Centro de Pesquisas Oncologicas — Florianópolis
• Fundação Amaral Carvalho - Jaú/ Sp — Jaú
• Instituto Nacional Do Câncer - Inca — Rio de Janeiro
• Icesp - Instituto Do Câncer Do Estado de São Paulo — São Paulo
• … и ещё 3 центра

Япония · 11 центров

Список центров уточняется — проверьте первичный протокол.

Китай · 10 центров

• The First Affiliated Hospital of Sun Yat-Sen University — Гуанчжоу
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• Shanghai Changzheng Hospital — Shang'ai
• Shanghai Ruijin Hospital — Шанхай
• Shanghai General Hospital — Шанхай
• West China Hopital of Sichuan University — Чэнду
• The Second Affiliated Hospital Zhejiang University School of Medical — Ханчжоу
• Beijing Cancer Hospital — Пекин
• … и ещё 2 центра

Франция · 8 центров

• Institut Bergonié — Bordeaux
• Centre Oscar Lambret — Lille
• Hôpital Léon Bérard — Lyon
• Hopital de La Timone — Marseille
• Hôpital Cochin — Paris
• INSTITUT de CANCEROLOGIE de l'Ouest — Saint-Herblain
• Iuct-Oncopole Institut Universitaire Du Cancer — Toulouse
• Institut Gustave Roussy — Villejuif

Германия · 8 центров

• Helios Klinikum Bad Saarow — Bad Saarow
• Charite Universitatsmedizin — Berlin
• Universitätsklinikum Carl Gustav Carus Dresden — Dresden
• Universitatsklinikum Hamburg-Eppendorf — Hamburg
• Universitätsmedizin Mannheim (Umm) — Mannheim
• Lmu Klinikum — München
• Ukm - Sarkom-Zentrum — Münster
• Universitaetsklinikum Ulm — Ulm

Италия · 8 центров

• Irccs Istituto Ortopedico Rizzoli — Bologna
• Irccs Fondazione Istituto Nazionale Dei Tumori — Milan
• San Luigi Gonzaga University Hospital of Turin — Orbassano
• Istituto Oncologico Veneto Iov - Irccs — Padova
• Aou Policlinico Paolo Giaccone — Palermo
• Ospedale Santo Stefano — Prato
• Policlinico Universitario Campus Biomedico — Roma
• … и ещё 1 центр

Испания · 7 центров

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Австралия · 6 центров

• Flinders Medical Centre — Bedford Park
• Chris O'Brien Lifehouse — Camperdown
• Chris O'Brien Lifehouse — Camperdown
• St Vincent'S Hospital Melbourne — Fitzroy
• Sir Charles Gairdner Hospital — Nedlands
• Princess Alexandra Hospital — Woolloongabba

Великобритания · 5 центров

Список центров уточняется — проверьте первичный протокол.

South Korea · 4 центра

Список центров уточняется — проверьте первичный протокол.

Бельгия · 3 центра

• Cliniques Universitaires St. Luc — Brussels
• U.Z. Gent — Ghent
• Centre Multidisciplinaire de Oncologie Medicale — Liège

Канада · 3 центра

• Alberta Health Services — Calgary
• University Health Network — Toronto
• Muhc Glen Site — Montreal

Нидерланды · 3 центра

Список центров уточняется — проверьте первичный протокол.

Дания · 2 центра

• Aarhus Universitetshospital — Aarhus
• Herlev & Gentofte Hospital — Herlev

Тайвань · 2 центра

Список центров уточняется — проверьте первичный протокол.

Пуэрто-Рико · 1 центр

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Публикации

• 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. PMID 40100120

Идентификаторы

NCT: NCT06127407 · CL3-95031-007

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗