This is an open-label, single-center Phase 0/2 study that will enroll up to 30 participants with newly diagnosed (N=12) and recurrent glioblastoma (N=18). The trial will be composed of a Phase 0 component (subdivided into Arm A, Arm B, and Arm C), and an Exploratory Phase 2 component. Participants with tumors demonstrating a PK response in the Phase 0 component of the study will graduate to an exploratory Phase 2 component that combines therapeutic dosing of pamiparib plus fractionated radiotherapy (for unmethylated MGMT promoter newly-diagnosed cases), pamiparib plus fractionated radiotherapy (for recurrent cases) or Olaparib plus fractionated radiotherapy (recurrent cases).

Inclusion Criteria:

1. Participants undergoing resection for a suspected newly diagnosed glioblastoma who are also planned to follow the standard regimen or;
2. Participants who have had a prior resection of histologically diagnosed glioblastoma (WHO grade IV), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy. Participants will also need to have radiation planned as part of the post-surgical treatment plan.
3. Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
4. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
5. Participant has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
6. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
7. Age ≥18 at time of consent
8. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982)
9. Ability to swallow oral medications.
10. Participant has adequate bone marrow and organ function
11. Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
12. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to treatment and agreement to use such a method during study participation and for an additional 6 months after the end of treatment administration.
13. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 6 months after the end of treatment administration. Avoid sperm donation for duration of the study and for an additional 6 months after the end of treatment administration.
14. Agreement to adhere to Lifestyle Considerations throughout study duration.
15. Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between last chemotherapy dose and Day 1 (provided the participant did not receive radiotherapy).
16. Females of child-bearing potential must agree not to breastfeed starting at screening, throughout the study period and for 6 months after final study drug administration

Exclusion Criteria:

1. Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise, that cannot be discontinued prior to surgery. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.

2. Pregnancy or lactation.

3. Known allergic reactions to components of the pamiparib capsule/olaparib.

4. Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1.

5. Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis.

6. Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.

7. Any of the following cardiovascular criteria:

   • Current evidence of cardiac ischemia
   • Current symptomatic pulmonary embolism
   • Acute myocardial infarction ≤ 6 months prior to Day 1
   • Heart failure of New York Heart Association Classification III or IV (see Section 13.2) ≤ 6 months prior to Day 1
   • Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to Day 1
   • Cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6 months prior to Day 1

8. Participant has myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML

9. Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).

10. Prior therapy with PARP inhibitors.

11. Treatment with another investigational drug or other intervention within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.

12. For Olaparib participants: Use or anticipated need for food and drugs known to be strong or moderate CYP3A inducers or inhibitors ≤10 days (or ≤5 half-lives, whichever is the shorter) prior to day 1.