Ivosidenib in participants with locally advanced or metastatic conventional chondrosarcoma untreated or previously treated with 1 or 2 systemic treatment regimens

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Apr 2025 → ongoing

Decision date (initial)

2025-07-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ADIR · Laboratorios Servier, S.L

External identifiers

EU CT number

2023-508507-20-00

ClinicalTrials.gov

NCT06127407

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Pharmacoeconomic, Safety

To assess the efficacy of ivosidenib treatment based on tumor assessments by a Blinded Independent Central Reviewer (BICR) in Grade 1 and Grade 2 participants

Secondary objectives 6

1. To assess the efficacy of ivosidenib treatment based on tumor assessments by a BICR in all randomized participants
2. To assess the efficacy of ivosidenib treatment based on Overall Survival (OS)
3. To assess the additional efficacy of ivosidenib treatment in Grade 1 and Grade 2 participants and all randomized participants
4. To assess the safety and tolerability of treatment with ivosidenib
5. To assess the impact of treatment on health-related quality of life (HRQoL) and health economic outcomes assessments
6. To evaluate the PK and PD of ivosidenib

Conditions and MedDRA coding

Locally advanced or metastatic conventional chondrosarcoma with an IDH1 mutation, untreated or previously treated with 1 or 2 systemic treatment regimens

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: - used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). - where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: - sponsored by Servier - with a first patient enrolled as of 1 January 2004 onwards - for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval. Supporting Materials: Study Protocol, SAP, ICF, CSR

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Have a histopathological diagnosis consistent with locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection or other local therapeutic options as per standard of care such as definitive radiotherapy for skull base lesions.
2. 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.
3. Have received 0 to 2 prior systemic treatment regimens in the advanced/metastatic setting for chondrosarcoma.
4. 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 (+3 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 (+3 weeks) before randomization.
5. Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or 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)
6. 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 13

1. Are unable to swallow oral medication.
2. Pregnant or lactating women.
3. Are participating in another interventional study at the same time; participation in noninterventional registries or epidemiological studies is allowed.
4. Have received prior therapy with an IDH1 inhibitor
5. Have received systemic anticancer therapy <2 weeks prior to randomization (for investigational or immune-based anticancer therapy <4 weeks).
6. Have received radiotherapy <2 weeks prior to randomization.
7. 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.
8. 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.
9. Have had major surgery within 4 weeks prior to randomization.
10. 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.
11. Have LVEF <40% by ECHO scan (or by other methods according to institutional practice) obtained within 28 days prior to randomization.
12. 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, familial history of sudden death or polymorphic ventricular arrhythmia). Participants with a bundle branch block combined with a prolonged QTcF interval may be permitted based on local cardiology assessment.
13. Have known medical history of progressive multifocal leukoencephalopathy (PML).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants

Secondary endpoints 14

1. PFS based on BICR assessment in all randomized participants
2. Overall survival (OS) in Grade 1 and Grade 2 participants
3. OS in all randomized participants
4. PFS based on Investigator assessment in Grade 1 and Grade 2 participants and in all randomised participants
5. Objective response (OR) (complete response(CR) or partial response (PR)) of anti-tumor activity (using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1) in Grade 1 and Grade 2 participants and in all randomised participants
6. Duration of response (DOR) in Grade 1 and Grade 2 participants and in all randomised participants
7. Time to response (TTR) in Grade 1 and Grade 2 participants and in all randomised participants
8. Disease control (DC) CR, PR, or stable disease (SD)) in Grade 1 and Grade 2 participants and in all randomised participants
9. Duration of disease control (DoDC) in Grade 1 and Grade 2 participants and in all randomised participants
10. Number of Adverse Events (AEs), Number of Serious Adverse Events (SAEs), Number of Adverse Events of Special Interest (AESIs), Number of Adverse Events (AEs) leading to discontinuation, treatment interruption, and dose reduction
11. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) score
12. European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) score
13. Patient-Reported Outcomes Measurement Information System (PROMIS) score
14. Ivosidenib and 2-hydroxyglutarate (2-HG) concentration in plasma

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Third parties 10

Locations

7 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 140 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

26 submissions — initial application plus substantial / non-substantial modifications