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

NCT02481154 | Completed Phase 1

• 1 other identifier: AG881-C-002
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

Glioma

Keywords

Glioma; IDH1; IDH2; Dual Mutation; AG-881

Outcome Measures

Primary Outcomes (2)

• Safety/Tolerability; incidence of adverse events

  Up to 26 weeks, on average

• Maximum Tolerated Dose and/or the recommended Phase II dose of AG881 in patients with advance solid tumors, including gliomas

  Up to 26 weeks, on average

Secondary Outcomes (4)

• Pharmacokinetic profiles including max concentration (Cmax), time to maximum concentration (Tmax), AUC, and elimination half-life

  Up to 26 weeks, on average

• Pharmacodynamic levels of AG-881

  Up to 26 weeks, on average

• Pharmacodynamic levels of 2-HG

  Up to 26 weeks, on average

• Clinical Activity according to RECIST v 1.1 (2009) for patients with solid tumors, by RANO (2010) criteria for patients with glioma

  Up to 26 weeks, on average

Study Arms (1)

AG881

EXPERIMENTAL

AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression, development of other unacceptable toxicity or Investigator discretion

Drug: AG881

Interventions

AG881 DRUG

AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression or development of other unacceptable toxicity

AG881

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be ≥18 years of age
• 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
• Patient must have evaluable disease by RECIST v1.1 for patients without glioma or by RANO or RANO LGG criteria for patients with glioma
• Patients with glioma must have a baseline brain MRI scan
• Patient must have archived primary tumor biopsies or surgical specimens, or biopsies of recurrent or metastatic samples
• Patient must be amenable to serial peripheral blood sampling, urine sampling, and tumor biopsies during the study
• Patient must be able to understand and willing to sign an informed consent
• Patient must have ECOG PS of 0 to 2
• Patient must have expected survival of ≥3 months
• 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
• 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
• 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
• Patient must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer
• 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

You may not qualify if:

• Patients who received systemic anticancer therapy or radiotherapy \<21 days prior to their first day of study drug administration
• 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.
• Patients with gliomas who have had prior treatment with bevacizumab (Avastin) are excluded
• Patients who are pregnant or breast feeding
• 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)
• 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
• Patients with a history of myocardial infarction within the 6 months prior to screening
• Patients with known unstable or uncontrolled angina pectoris
• Patients with a known history of severe and/or uncontrolled ventricular arrhythmias
• 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)
• 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.
• Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
• Patients with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
• 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
• Glioma patients with evidence of intracranial or intratumoral hemorrhage either by MRI or CT scan

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead

Study Sites (9)

UCLA Oncology Center

Los Angeles, California, 90024, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 75390, United States

Location

Related Publications (1)

• Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA 3rd, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY. Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. Clin Cancer Res. 2021 Aug 15;27(16):4491-4499. doi: 10.1158/1078-0432.CCR-21-0611. Epub 2021 Jun 2.

  PMID: 34078652 DERIVED

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 25, 2015
• Study Start: June 1, 2015
• Primary Completion: October 17, 2022
• Study Completion: June 19, 2024
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

US (9)