For Healthcare Professionals

Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation

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About the study

This study evaluates the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in Gliomas, that harbor an IDH1 and/or IDH2 mutation.
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Who can take part

You may be eligible to participate in the study if you meet the following criteria:

INCLUSION CRITERIA

  1. Patient must be ≥18 years of age
  2. Patient must have histologically or cytologically confirmed solid tumor, including glioma, with documented IDH1 and/or IDH2 gene-mutation. Patients in the dose escalation phase must have disease that has recurred or progressed following standard therapy and/or therapy with an inhibitor of mutant IDH1 and/or IDH2, or that has not responded to this therapy. Patients in the expansion phase may have previously untreated disease
  3. Patient must have evaluable disease by RECIST v1.1 for patients without glioma or by RANO or RANO LGG criteria for patients with glioma
  4. Patients with glioma must have a baseline brain MRI scan
  5. Patient must have archived primary tumor biopsies or surgical specimens, or biopsies of recurrent or metastatic samples
  6. Patient must be amenable to serial peripheral blood sampling, urine sampling, and tumor biopsies during the study
  7. Patient must be able to understand and willing to sign an informed consent
  8. Patient must have ECOG PS of 0 to 2
  9. Patient must have expected survival of ≥3 months
  10. Patient must have adequate bone marrow function as evidenced by absolute neutrophil count ≥1.5 ×10^9/L; hemoglobin >9 g/dL (Patients are allowed to be transfused to this level); platelets ≥75 × 10^9/L
  11. Patient must have adequate hepatic function as evidenced by: Serum total bilirubin ≤1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement; Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤2.5 × ULN. For patients with bone metastases and/or suspected disease-related liver or biliary involvement, AST, ALT and ALP must be ≤5 × ULN
  12. Patient must have adequate renal function as evidenced by: Serum creatinine ≤2.0 × ULN or Creatinine clearance >40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimated: (140-Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine
  13. Patient must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer
  14. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to first study drug administration. Patients with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not experienced natural menopause (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., have had menses at any time in the preceding 24 consecutive months). Women with reproductive potential as well as fertile men and their partners who are female with reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study, and for 90 days (females and males) following the last dose of AG 881

EXCLUSION CRITERIA

  1. Patients who received systemic anticancer therapy or radiotherapy <21 days prior to their first day of study drug administration
  2. Patients who received an investigational agent (including AG-120 or AG-221) <14 days prior to their first day of study drug administration. In addition, the first dose of AG-881 should not occur before a period ≥5 half-lives of the investigational agent (other than AG-120 or AG-221) has elapsed.
  3. Patients with gliomas who have had prior treatment with bevacizumab (Avastin) are excluded
  4. Patients who are pregnant or breast feeding
  5. Patients 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, patients with tumor fever may be enrolled)
  6. Patients 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 obtained within approximately 28 days of C1D1
  7. Patients with a history of myocardial infarction within the 6 months prior to screening
  8. Patients with known unstable or uncontrolled angina pectoris
  9. Patients with a known history of severe and/or uncontrolled ventricular arrhythmias
  10. Patients with 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)
  11. Patients taking medications that are known to prolong the QT interval unless they can be transferred to other medications within ≥5 half-lives prior to dosing, or unless the medications can be properly monitored during the study.
  12. Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
  13. Patients with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
  14. Patients 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 1 month of first dose
  15. Glioma patients with evidence of intracranial or intratumoral hemorrhage either by MRI or CT scan
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Study Locations

Enter your ZIP code/Postal code/PIN code to locate study sites near you:

How to Apply


Contact the study center to learn if this study is a good match for you.
Phone iconCall (617) 649-8600Email iconEmail Study Center

Study’s details


Contition

Cholangiocarcinoma,Chondrosarcoma,Glioma

Age

18+

Phase

Phase 1

Participants needed

95

Est. Completion Date

Jun 2023

Treatment type

Interventional


Sponsor

Servier

ClinicalTrials.gov identifier

NCT02481154

Study number

AG881-C-002

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