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

Inclusion Criteria:

• Arm A Only: Participants must have histologically confirmed World HealthOrganization (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 Bmust have magnetic resonance imaging (MRI) confirming progressive disease; re-biopsyis encouraged, but not required at the time of recurrence for confirmation.

• Participants with a primary spinal tumor, secondary glioma, or multifocal disease inthe brain, but without evidence of diffuse leptomeningeal spread, are eligible. Incases where there are questions about multifocality versus diffuse leptomeningealspread, the study chair or co-chair must be contacted to make a final decision oneligibility.

• Participants must have IDH1 or IDH2 mutation associated with neomorphic activity ofthe encoded proteins.

• Participants must be willing to provide archival formalin-fixed embedded (FFPE) andfrozen tissue specimens for biomarker studies if available.

• Participants in Arm A must have been treated with maximal safe resection of primarytumor followed by adjuvant radiation therapy (RT). Treatment with TMZ duringradiation 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 surgeryalone are eligible. Any number of prior therapies are allowed.

• High grade glioma (HGG) participants enrolled on Arm B must have been treatedwith a minimum of maximal safe resection of primary tumor followed by adjuvantRT prior to recurrence. Any number of prior therapies are allowed.

• Participants must have fully recovered from the acute toxic effects of all priorchemotherapy, immunotherapy, or radiotherapy prior to entering this study.

• Myelosuppressive chemotherapy: participants must have received their last dose ofknown myelosuppressive anticancer chemotherapy at least three weeks prior to studyregistration or at least six weeks if nitrosourea.

• Biologic agent: participants must have recovered from any toxicity related tobiologic agents and received their last dose >= 7 days prior to study registration.

• For agents that have known adverse events occurring beyond 7 days afteradministration, this period must be extended beyond the time during whichadverse events are known to occur. The duration of this interval should bediscussed with the study chair.

• For biologic agents that have a prolonged half-life, the appropriate intervalsince last treatment should be discussed with the study chair prior toregistration.

• Monoclonal antibody treatment: at least three half-lives must have elapsed prior toregistration, 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 ofradiation 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 trueprogression versus pseudo-progression can be challenging when imaging modalities areexclusively used, and thus an additional resection is encouraged if clinicallyindicated.

• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3.

• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receivingplatelet 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 creatinineclearance >= 50 mL/min (calculated using the institutional standard method).

• Total serum bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit ofnormal (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 inducinganticonvulsants and well controlled.

• Participants who have neurological deficits should have deficits that are stable fora minimum of 1 week prior to registration.

• Corticosteroids: Participants who are receiving dexamethasone must be on a stable ordecreasing dose for at least 1 week prior to registration.

• The effects of BGB-290 on the developing human fetus are unknown. For this reasonand because alkylating agents (such as TMZ) are known to be teratogenic, women ofchild-bearing potential and men must agree to use adequate contraception (hormonalor barrier method of birth control; abstinence) prior to study entry, for theduration of study participation and 4 months after completion of BGB-290 or TMZadministration. Should a woman become pregnant or suspect she is pregnant while sheor her partner is participating in this study, she should inform her treatingphysician immediately.

• Participants must be able to swallow capsules.

• Participants must have the ability to undergo serial MRI scans (computerizedtomography [CT] cannot substitute for MRI).

• A legal parent/guardian or patient must be able to understand, and willing to sign,a written informed consent and assent document, as appropriate.

• Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants =< 16 years of age. Participants who are unable to walk because of paralysis, butwho are up in a wheelchair, will be considered ambulatory for the purpose ofassessing the performance score.

Exclusion Criteria:

• Participants who are receiving any other investigational agents at any time may notbe 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, ormelena =< 6 months prior to day 1.

• Participants on therapeutic anti-coagulation with heparin, warfarin, or otheranticoagulants:

• Use of low-dose aspirin and/or non-steroidal anti-inflammatory agents areallowed.

• Use of thrombolytic to establish patency of indwelling venous catheters isallowed.

• Prophylactic anticoagulation for venous access devices is allowed as long asinstitutional 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 thisstudy.

• Unresolved acute effects of any prior therapy of grade >= 2, except for adverseevents (AEs) not constituting a safety risk by investigator judgement.

• Use =< 10 days (or =< 5 half-lives, whichever is shorter) prior to day 1 oranticipated 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 orbiologic composition to TMZ or pamiparib (BGB-290).

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.

• Female participants of childbearing potential must not be pregnant orbreast-feeding. Female participants of childbearing potential must have a negativeserum or urine pregnancy test within 7 days of first dose.

• Human immunodeficiency virus (HIV)-positive participants on combinationantiretroviral therapy are ineligible because of the potential for pharmacokineticinteractions with pamiparib (BGB-290) and TMZ. In addition, these participants areat increased risk of lethal infections when treated with marrow-suppressive therapy.

• Participants with inability to return for follow-up visits or obtain follow-upstudies required to assess toxicity to therapy.