IVY-P3-24-021: A trial recruiting people with newly diagnosed, MGMT unmethylated glioblastoma (GBM) to evaluate whether treatment with targeted therapy is more effective than chemotherapyA Phase 3, Open-label, Randomized 2-arm Study Comparing the Clinical Efficacy and Safety of Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma

Exclusion

• 1. Presence of metastatic or predominant leptomeningeal disease.
• 2. Current active pneumonitis or any history of pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study.
• 3. Participant is at an increased bleeding risk due to concurrent conditions (e.g., major injuries or major surgery within the past 28 days prior to start of study treatment with the exception of tumor resection).
• 4. Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
• 5. Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. NOTE: Stable noncirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones), hepatobiliary involvement of malignancy, or chronic stable HBV infection (in a participant for whom HDV infection has been excluded) or chronic HCV infection is acceptable if the participant otherwise meets entry criteria.

• 6. Known human immunodeficiency virus (HIV) unless participants meet all of the following criteria:

  • Cluster of differentiation 4 ≥350/µL and viral load <400 copies/mL.
  • No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment.
  • No history of HIV-associated malignancy for the past 5 years.
  • Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV [NIH, 2021] started >4 weeks prior to study enrollment.
• 7. MDS/AML or with features suggestive of MDS/AML.
• 8. History of another malignancy within 2 years prior to registration. Participants with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Participants with a history of other malignancies are eligible if they have been treated with curative intent or continuously disease free for at least 2 years after definitive primary treatment.
• 9. Prior history of posterior reversible encephalopathy syndrome (PRES).
• 10. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study requirements and/or follow-up procedures.
• 11. Inability to undergo MRI brain with IV contrast.
• 12. Biopsy and/or resection (whichever is later) occurring >6 weeks prior to planned RT start date.
• 13. Surgical wound complication recovery at the time of enrollment.
• 14. Known hypersensitivity to the components of niraparib, TMZ, or their formulation excipients.
• 15. Known hypersensitivity to dacarbazine (DTIC).
• 16. Prior therapy with PARP inhibitors for systemic cancer.
• 17. Received a live vaccine within 30 days before the planned start of study intervention. Coronavirus disease 2019 (COVID-19) vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.
• 18. Received a transfusion (platelets or red blood cells) or colony-stimulating factors (e.g., granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks of the planned start of study intervention.
• 19. Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product.
• 20. Treatment with tumor treating fields (e.g., Optune) for GBM.
• 21. Presence of known isocitrate dehydrogenase (IDH) mutation.
• 22. Presence of known H3 mutation.
• 23. Previous diagnosis of WHO Grade 2 or 3 glioma.