Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Neoplasms by Histologic Type

Gliosarcoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Tumor, Adult

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Pamiparib

Enzyme Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Alkylating Agents

Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.

Participants with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ).

Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.

Administered as specified in the treatment arm

Radiation

Study Director

The primary objective of this study is to evaluate the safety, efficacy and clinical activity of Pamiparib in combination with radiation therapy (RT) and/or temozolomide (TMZ) in participants with newly diagnosed or recurrent/refractory 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.

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

A Phase 1b/2 Study to Assess the Safety, Tolerability and Efficacy of BGB-290 in Combination With Radiation Therapy (RT) and/or Temozolomide (TMZ) in Subjects With First-line or Recurrent/Refractory Glioblastoma

A DLT is defined as one of the following toxicities occurring during the DLT assessment window:

Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting \>7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting \> 3 days and requiring transfusion, or any decreased platelet count \<15,000/mm3/ \<15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)

A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first.

An SAE is any untoward medical occurrence that, at any dose meets at least one of the following criteria: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is considered a significant medical AE based on medical judgment.

Modified DCR is defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) per RANO criteria as the response assessment at the end-of-treatment (EOT) visit.

ORR (objective response rate) is defined as percentage of participants with best overall response of CR or PR per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).

Data shows the number of participants who received treatment for the given number of cycles.

The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).

DCR is defined as the percentage of participants with best overall response of CR, PR or SD per RANO criteria. CR or PR will be confirmed by a subsequent tumor assessment at least four weeks apart

ORR is defined as percentage of participants with best overall response of CR or PR per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).

Clinical benefit rate (CBR) is defined as the percentage of participants with best overall response of CR, PR or SD ≥ 24 weeks per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).

DOR is defined as the time from the date of the earliest documented response to disease progression or death for any cause whichever occurs earlier (confirmed by a subsequent tumor assessment at least four weeks apart).

PFS is defined as the time from the first dose date to disease progression per RANO criteria or death, whichever occurs first.

OS is defined as the time from the first dose date to date of death for any cause.

A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first. An SAE is any untoward medical occurrence that, at any dose meets at least one of the following criteria: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is considered a significant medical AE based on medical judgment.

BeiGene USA, Inc.

A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first.

Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks

Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks

Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks

Arm A: DE-Pamiparib 4 Wks + RT 6 Wks

Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks

Arm A: DE- Pamiparib 6Wks + RT 6 Wks

Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks

Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5

Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide

Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21

Arm C: DE - Pamiparib + Temozolomide 20 mg

Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21

Arm C: DE - Pamiparib + Temozolomide 40 mg

Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7

Arm C: E- Pamiparib + Temozolomide 60 mg

Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Unknown/Not Reported

Race/Ethnicity, Customized

The Safety Analysis Set includes all participants who received any study treatment (pamiparib, RT, and/or TMZ). The Safety Analysis Set was used for all efficacy and safety analyses.

Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE

Participants with At Least 1 TEAE

TEAE with Grade 3 or Higher

Treatment Emergent SAEs

TEAE Leading to Death

Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE

Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements

The Efficacy Analysis Set (Arm A) includes participants in the Safety Analysis Set who had a tumor assessment at baseline and at End of Treatment unless discontinued treatment or study early due to disease progression or death prior to tumor assessment. Participants with available data were included in the analysis.

Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria

The Efficacy Analysis Set (Arm C) includes participants in the Safety Analysis Set who had measurable disease at baseline and at least one postbaseline tumor assessment unless discontinued treatment or study early due to disease progression or death prior to tumor assessment. Participants with available data were included in the analysis.

Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria

<1 cycle

1 cycle

2 cycles

3 cycles

4 cycles

5 cycles

6 cycles

7 cycles

>7 cycles

Phase 1b Arm C: Number of Cycles of Treatment Received by Participants

Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant

The Pharmacokinetic (PK) Analysis Set includes all participants for whom valid pamiparib PK parameters can be estimated. Participants with available data were included in the analysis.

Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib

Efficacy Analysis Set; Participants with available data were included in the analysis

Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria

Arm C: DE- Pamiparib + Temozolomide 20 mg

Efficacy Analysis Set; Participants with available data were included in the analysis.

Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria

Efficacy Evaluable Analysis Set; Participants with available data were included in the analysis.

Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria

Efficacy Analysis Set; participants with available data were included in the analysis

Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria

Efficacy Analysis Set; Only the participants with objective responses were included in DOR analysis.

Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria

Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria

Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)

Participants with at Lease 1 TEAE

Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements

Safety Analysis Set; For Arm A Only participants who entered the maintenance phase were included in the analysis as per protocol.

Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants

Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant

Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 milligrams (mg) pamiparib orally twice daily (BID) for 2 weeks in combination with up to 60 Gy radiation for 6 weeks

Spots Global Cancer Trial Database for neoplasms, central nervous system neoplasms, neoplasms by histologic type, neoplasms by site