BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas

Running, not enrolling · Phase 1

Conditions studied: Glioblastoma, IDH1 Gene Mutation, IDH2 Gene Mutation, Low Grade Glioma, Malignant Glioma, Recurrent Glioblastoma, Recurrent WHO Grade II Glioma, Recurrent WHO Grade III Glioma, WHO Grade II Glioma, WHO Grade III Glioma

In brief

This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BGB-290 and temozolomide may work better in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma.

Key facts

Study ID

NCT03749187

Run by

University of California, San Francisco

People needed

78

Starts

2019-04-03

Expected to finish

2029-07-30

Last updated by the study team

2026-03-13

Who can join

Age: 13 and older, up to 39. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Arm A Only: Participants must have histologically confirmed World Health Organization (WHO) grade III-IV newly diagnosed IDH1/2-mutant glioma.
• Arm B Only: WHO grades I-IV recurrent IDH1/2 mutant glioma. Participants in Arm B must have magnetic resonance imaging (MRI) confirming progressive disease; re-biopsy is encouraged, but not required at the time of recurrence for confirmation.
• Participants with a primary spinal tumor, secondary glioma, or multifocal disease in the brain, but without evidence of diffuse leptomeningeal spread, are eligible. In cases where there are questions about multifocality versus diffuse leptomeningeal spread, the study chair or co-chair must be contacted to make a final decision on eligibility.
• Participants must have IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins.
• Participants must be willing to provide archival formalin-fixed embedded (FFPE) and frozen tissue specimens for biomarker studies if available.
• Participants in Arm A must have been treated with maximal safe resection of primary tumor followed by adjuvant radiation therapy (RT). Treatment with TMZ during radiation is allowed but not required.
• Participants in Arm B must have been treated with maximal safe resection of tumor.
• Lower grade glioma (LGG) participants who progressed after initial surgery alone are eligible. Any number of prior therapies are allowed.
• High grade glioma (HGG) participants enrolled on Arm B must have been treated with a minimum of maximal safe resection of primary tumor followed by adjuvant RT prior to recurrence. Any number of prior therapies are allowed.
• Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Myelosuppressive chemotherapy: participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if nitrosourea.
• Biologic agent: participants must have recovered from any toxicity related to biologic agents and received their last dose >= 7 days prior to study registration.
• For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
• For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the study chair prior to registration.
• Monoclonal antibody treatment: at least three half-lives must have elapsed prior to registration, and participants on bevacizumab must have received their last dose >= 32 days prior to study registration.
• Participants in Arm A should begin therapy with TMZ and BGB-290 after completion of radiation therapy and when all other eligibility criteria are met.
• For participants in Arm B, patients must not have received radiation therapy within 4 weeks prior to the initiation of study treatment. Post-RT, the diagnosis of true progression versus pseudo-progression can be challenging when imaging modalities are exclusively used, and thus an additional resection is encouraged if clinically indicated.
• Peripheral absolute neutrophil count (ANC) >= 1000/mm\^3.
• Platelet count >= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
• Hemoglobin >= 9 g/dL.
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance >= 50 mL/min (calculated using the institutional standard method).
• Total serum bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN).
• Aspartate and alanine aminotransferase (AST and ALT) =< 3 x ULN.
• Serum albumin >= 2 g/dL.
• Participants with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.

You may not qualify if…

• Participants who are receiving any other investigational agents at any time may not be enrolled.
• Participants who have received a PARP inhibitor previously.
• Participants with active infection requiring antibiotics at time of therapy start.
• Participants with other diagnosis of malignancy.
• Participants with clinically significant active bleeding disorder, hemoptysis, or melena =< 6 months prior to day 1.
• Participants on therapeutic anti-coagulation with heparin, warfarin, or other anticoagulants:
• Use of low-dose aspirin and/or non-steroidal anti-inflammatory agents are allowed.
• Use of thrombolytic to establish patency of indwelling venous catheters is allowed.
• Prophylactic anticoagulation for venous access devices is allowed as long as institutional normalized ratio (INR) is =< 1.5 and partial thromboplastin time (aPTT) =< 1.5 x institutional ULN.
• Use of low-molecular weight heparin is allowed.
• Participants with known disseminated leptomeningeal disease.
• Participants with diffuse intrinsic pontine glioma (DIPG) are not eligible for this study.
• Unresolved acute effects of any prior therapy of grade >= 2, except for adverse events (AEs) not constituting a safety risk by investigator judgement.
• Use =< 10 days (or =< 5 half-lives, whichever is shorter) prior to day 1 or anticipated need for food or drugs known to be strong or moderate Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TMZ or pamiparib (BGB-290).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose.
• Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pamiparib (BGB-290) and TMZ. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Participants with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• University of California, San Francisco — San Francisco, California, United States
• Yale University — New Haven, Connecticut, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center — Hackensack, New Jersey, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States

Full record on ClinicalTrials.gov

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