A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma

An open-label, multiple-dose, dose-escalation study to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of Pamiparib in combination with radiation therapy (RT) and/or TMZ.

In dose escalation/Phase 1b, Pamiparib will be combined with RT (Arm A) or RT and TMZ (Arm B) in participants with newly diagnosed unmethylated glioblastoma (GBM) and in Arm C of the study Pamiparib will be combined with TMZ in participants with methylated or unmethylated recurrent/refractory GBM.

The dose expansion/Phase 2 phase will enroll up to 4 cohorts: participants with newly diagnosed unmethylated GBM in Arms A and B, and 2 cohorts of participants with recurrent/refractory GBM grouped by O-6-methylguanine-DNA methyltransferase (MGMT) status - unmethylated or methylated - in Arm C.

Participants in Arms A and B are treated until completion of RT and participants in Arm C may continue treatment in the absence of safety concerns and disease progression.

Key Inclusion Criteria: All participants

• Age ≥ 18 years old.
• Confirmed diagnosis of glioblastoma (WHO Grade IV).
• Agreement to provide archival tumor tissue for exploratory biomarker analysis
• Ability to undergo serial MRIs.
• Eastern Cooperative Oncology Group (ECOG) status ≤ 1.
• Adequate hematologic and end-organ function
• Females of childbearing potential and non-sterile males must agree to use highly effective methods of birth control throughout the course of study and at least up to 6 months after last dosing.
• Ability to swallow whole capsules.

Participants in Arms A and B (not Arm C) must meet inclusion criteria # 9 - 11:

• No previous treatment for GBM except surgery.
• Able to start radiation therapy ≤ 49 days after surgery but ≥ 14 days after a biopsy or ≥28 days after an open biopsy or craniotomy with adequate wound healing.
• Documented unmethylated MGMT promoter status.

Participants in Arm C Escalation (Phase 1b) must meet inclusion criteria # 12 - 15:

• Documentation of MGMT promoter status
• No prior systemic chemotherapy other than TMZ for GBM.
• Histologically confirmed secondary glioblastoma
• Disease that is evaluable or measurable as defined by Response Assessment in Neuro-Oncology (RANO) criteria

Participants in Arm C Expansion (Phase 2), must meet criteria # 16 - 18:

• Histologically confirmed de novo (primary) glioblastoma with unequivocal first progressive disease (PD) after RT with concurrent/adjuvant TMZ chemotherapy
• Disease that is measurable as defined by RANO criteria
• Documentation of MGMT promoter status

Key Exclusion Criteria: All participants

• Prior chemotherapy, biologic therapy, immunotherapy or investigational agents ≤21 days prior to start of study treatment.
• Toxicity of ≥ Grade 2 from prior therapy.
• Major surgery or significant other injury ≤ 4 weeks prior to start of study treatment.
• History of other active malignancies within 2 years with exception of (i) adequately treated in situ cancer of the cervix, (ii) non-melanoma skin cancer, or (iii) localized adequately treated cancer with curative intent or malignancy diagnosed > 2 years ago with no evidence of disease and no treatment ≤ 2 years prior to study treatment.
• Active infection requiring systemic treatment.
• Known human immunodeficiency virus (HIV) or active viral hepatitis.
• Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease, ventricular arrhythmia or Cerebrovascular Accident (CVA) ≤ 6 months prior to start of treatment.
• Active clinically significant gastrointestinal disease.
• Active bleeding disorder ≤ 6 months prior to start of treatment.
• Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants.
• Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.
• Pregnant or nursing females.
• Significant intercurrent illness that may result in participant's death prior to death from glioblastoma.

Arms B and C Only:

• Known hypersensitivity to any component of TMZ or decarbazine (DTIC).
• Have hereditary problems of galactose intolerance

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.