Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation

Completed · Phase 1

Conditions studied: Cholangiocarcinoma, Chondrosarcoma, Glioma, Other Advanced Solid Tumors

In brief

The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced solid tumors, including glioma, that harbor an IDH1 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where four arms of patients will receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Anticipated time on study treatment is until disease progression, unacceptable toxicity occurs or at Investigator discretion.

Key facts

Study ID

NCT02073994

Run by

Institut de Recherches Internationales Servier

People needed

174

Starts

2014-03-01

Expected to finish

2024-01-04

Last updated by the study team

2026-02-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Subjects who received systemic anticancer therapy or radiotherapy <21 days prior to their first day of study drug administration.
• Subjects who received an investigational agent <14 days prior to their first day of study drug administration. In addition, the first dose of AG-120 should not occur before a period ≥5 half-lives of the investigational agent has elapsed.
• Subjects taking the following sensitive cytochrome P450 (CYP) 3A4 substrate medications are excluded from the study unless they can be transferred to other medications prior to enrolling: alfentanil, aprepitant, budesonide, buspirone, conivaptan, darifenacin, darunavir, dronedarone, eletriptan, eplerenone, felodipine, indinavir, fluticasone, lopinavir, lovastatin, lurasidone, maraviroc, midazolam, nisoldipine, quetiapine, saquinavir, sildenafil, simvastatin, tolvaptan, tipranavir, triazolam, ticagrelor, vardenafil and/or the CYP2B6 substrates: bupropion, efavirenz.
• Subjects taking the following P-glycoprotein (P-gp) transporter-sensitive substrate medications are excluded from the study unless they can be transferred to other medications prior to enrolling: aliskiren, ambrisentan, colchicine, dabigatran etexilate, digoxin, fexofenadine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, and tolvaptan.
• Subjects for whom potentially curative anticancer therapy is available.
• Subjects who are pregnant or breast feeding.
• Subjects with an active severe infection that required anti-infective therapy or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled).
• Subjects with known hypersensitivity to any of the components of AG-120.
• Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1.
• Subjects with a history of myocardial infarction within the last 6 months.
• Subjects with known unstable or uncontrolled angina pectoris.
• Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
• Subjects with heart-rate corrected QT (QTc) interval ≥ 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion.
• Subjects taking medications that are known to prolong the QT interval (see Section 9.11.3).
• Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
• Subjects with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study.
• Subjects with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
• Subjects with brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including those used to control symptoms, within 2 months of first dose. Subjects with glioma who are on a stable, steroid dosing regimen 5 days prior to the screening MRI may be permitted to enroll with Medical Monitor approval.
• Subjects with a history of Grade 4 astrocytoma (applicable only to subjects enrolled in the dose expansion non-enhancing glioma cohort).

Where it is running

• Study site — Scottsdale, Arizona, United States
• Study site — Los Angeles, California, United States
• Study site — Aurora, Colorado, United States
• Study site — Miami, Florida, United States
• Study site — Baltimore, Maryland, United States
• Study site — Boston, Massachusetts, United States
• Study site — New York, New York, United States
• Study site — Nashville, Tennessee, United States
• Study site — Dallas, Texas, United States
• Study site — Houston, Texas, United States
• Study site — San Antonio, Texas, United States
• Study site — Villejuif, France

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.