CompletedNCT03150862Updated Feb 4, 2025Results posted

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

A Phase 1/2 interventional study of Pamiparib and TMZ in Brain and Central Nervous System Tumors, sponsored by BeiGene USA, Inc.. Completed at 22 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-04.

Sponsored by BeiGene USA, Inc. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 116
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Read the detailed description

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.

Conditions studied

Brain and Central Nervous System Tumors

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Keywords

Adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, glioma neoplasms
recurrent adult brain tumor
neoplasms, central nervous system neoplasms, neoplasms by histologic type, neoplasms by site
astrocytoma
neuroepithelial
neuroectodermal tumors
germ cell and embryonal
antineoplastic agents
glandular and epithelial
nerve tissue, nervous system diseases
temozolomide
BGB-290
alkylating, alkylating agents
molecular mechanisms of pharmacological action
Poly(ADP-ribose) polymerase inhibitors
enzyme inhibitors

In context

Glioblastoma

1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.

This study's enrollment of 116 is above the median of 36 across 1,618 interventional studies indexed under Glioblastoma.

Browse Glioblastoma studies →

Lead sponsor

This is the only study on the registry with BeiGene USA, Inc. as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 116 participants (actual)

Study arms

Experimental
Arm A (Dose Escalation)
Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.
Drug: Pamiparib · Radiation: Radiation
Experimental
Arm B (Dose Escalation)
Participants with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ).
Drug: Pamiparib · Drug: TMZ · Radiation: Radiation
Experimental
Arm A (Dose Expansion)
Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.
Drug: Pamiparib · Radiation: Radiation
Experimental
Arm C (Dose Escalation)
Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.
Drug: Pamiparib · Drug: TMZ
Experimental
Arm C (Dose Expansion-Cohorts C1 and C2)
Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.
Drug: Pamiparib · Drug: TMZ

Interventions

DrugPamiparib
Administered as specified in the treatment arm
Also known as: BGB-290
DrugTMZ
Administered as specified in the treatment arm
RadiationRadiation
Up to 60 Gy (total) over 6 - 7 weeks

What researchers measure

Primary outcomes

Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE
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)
Time frame: Arm A:Day 1 Pamiparib dose until 4 weeks after the last RT; Arm B: Day 1 of Pamiparib and Temozolomide until 4 weeks after the last RT; Arm C: 1st cycle of 28 days
Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE
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.
Time frame: From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)
Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Time frame: From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)
Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria
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.
Time frame: From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)
Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria
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).
Time frame: From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Phase 1b Arm C: Number of Cycles of Treatment Received by Participants
Data shows the number of participants who received treatment for the given number of cycles.
Time frame: From the date of first dose up to EOS visit ( up to 3 years and 7.5 months)
Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant
The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
Time frame: From the date of first dose until EOS visit (up to 3 years and 7.5 months)

Secondary outcomes

Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib
Time frame: Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy
Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria
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.
Time frame: From the date of first dose up to first documentation of disease progression while participant is alive (approximately 3 years and 7.5 months)
Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria
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
Time frame: From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria
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).
Time frame: From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)
Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria
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).
Time frame: From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria
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).
Time frame: From first documentation of CR or PR to first documentation of disease progression or death (up to 3 years and 7.5 months)
Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria
PFS is defined as the time from the first dose date to disease progression per RANO criteria or death, whichever occurs first.
Time frame: From the date of first dose up to first documentation of disease progression or death (up to 3 years and 7.5 months)
Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)
OS is defined as the time from the first dose date to date of death for any cause.
Time frame: From the date of first dose up to the date of death (up to 3 years and 7.5 months)
Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)
Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Time frame: From the date of first dose up to EOS visit (up to 3 years and 7.5 months)
Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants
Data shows the number of participants who received treatment for the given number of cycles.
Time frame: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant
The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
Time frame: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)

Results

Posted May 31, 2022

Participant flow

This study consisted of a dose escalation phase and a dose expansion phase. A total of 116 participants were recruited in Netherlands, Switzerland and United States.

Participant flow — Overall Study
Milestone	Arm A: Dose Escalation (DE) - Pamiparib 2 Weeks (Wks) + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
Started	3	8	9	40	9	9	8	30
Completed	0	0	0	0	0	0	0	0
Not completed	3	8	9	40	9	9	8	30
Withdrew: Death	2	7	8	27	4	8	6	21
Withdrew: Withdrawal by subject	1	1	0	3	1	1	1	3
Withdrew: Lost to follow-up	0	0	1	0	0	0	0	2
Withdrew: Sponsor's decision	0	0	0	10	3	0	1	1
Withdrew: Change in methylation status	0	0	0	0	1	0	0	0
Withdrew: Roll over in to long term extension	0	0	0	0	0	0	0	1
Withdrew: Progressive disease	0	0	0	0	0	0	0	2

Outcome measures

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

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)

Time frame:: Arm A:Day 1 Pamiparib dose until 4 weeks after the last RT; Arm B: Day 1 of Pamiparib and Temozolomide until 4 weeks after the last RT; Arm C: 1st cycle of 28 days
Reported as:: Number · participants

Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE
participants	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg
Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE	0	0	2	1	0	3

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

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.

Time frame:: From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)
Reported as:: Number · participants

Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE
participants	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg
Participants with At Least 1 TEAE	3	8	9	9	9	8
TEAE with Grade 3 or Higher	1	3	4	4	5	7
Treatment Emergent SAEs	0	2	2	2	4	3
TEAE Leading to Death	0	0	0	0	0	0

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

Time frame:: From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)
Reported as:: Number · Number of participants

Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Number of participants	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg
Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements	0	0

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

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.

Time frame:: From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)
Reported as:: Number · Percentage of participants

Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria
Percentage of participants	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks
Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria	65.6 (46.8 to 81.4)

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

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).

Time frame:: From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Reported as:: Number · Percentage of participants

Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria
Percentage of participants	Arm C: E- Pamiparib + Temozolomide 60 mg
Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria	10.7 (2.3 to 28.2)

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

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

Time frame:: From the date of first dose up to EOS visit ( up to 3 years and 7.5 months)
Reported as:: Number · participants

Phase 1b Arm C: Number of Cycles of Treatment Received by Participants
participants	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg
<1 cycle	2	3
1 cycle	4	0
2 cycles	1	2
3 cycles	0	1
4 cycles	1	0
5 cycles	1	0
6 cycles	0	0
7 cycles	0	0
>7 cycles	0	2

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

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

Time frame:: From the date of first dose until EOS visit (up to 3 years and 7.5 months)
Reported as:: Mean · milligrams/Day

Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant
milligrams/Day	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg
Pamiparib	97.5 ± 25.41	107.6 ± 14.65
TMZ	13.6 ± 1.88	28.2 ± 10.80

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

Time frame:: Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy
Reported as:: Mean · ng/mL

Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib
ng/mL	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib	891.3 ± 444.51	1817.0 ± 1226.53	1848.3 ± 784.38	2239.9 ± 1011.07	2134.3 ± 953.06	1893.3 ± 718.46	1550.8 ± 1422.55	1500.2 ± 943.35

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

Time frame:: From the date of first dose up to first documentation of disease progression while participant is alive (approximately 3 years and 7.5 months)
Reported as:: Number · Percentage of participants

Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria
Percentage of participants	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide
Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria	66.7 (9.4 to 99.2)	100.0 (54.1 to 100.0)	42.9 (9.9 to 81.6)	80.0 (28.4 to 99.5)

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

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

Time frame:: From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Reported as:: Number · Percentage of participants

Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria
Percentage of participants	Arm C: DE- Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg
Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria	55.6 (21.2 to 86.3)	71.4 (29.0 to 96.3)

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

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).

Time frame:: From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)
Reported as:: Number · Percentage of participants

Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria
Percentage of participants	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide
Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria	0 (0.0 to 70.8)	16.7 (0.4 to 64.1)	0 (0.0 to 41.0)	3.1 (0.1 to 16.2)	0 (0.0 to 52.2)

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

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).

Time frame:: From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Reported as:: Number · Percentage of participants

Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria
Percentage of participants	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria	0 (0.0 to 70.8)	33.3 (4.3 to 77.7)	0 (0.0 to 41.0)	37.6 (21.1 to 56.3)	40.0 (5.3 to 85.3)	0 (0.0 to 33.6)	28.6 (3.7 to 71.0)	17.9 (6.1 to 36.9)

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

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).

Time frame:: From first documentation of CR or PR to first documentation of disease progression or death (up to 3 years and 7.5 months)
Reported as:: Median · Months

Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria
Months	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria	—	6.44 (NA to NA)	—	10.32 (NA to NA)	—	—	11.7 (NA to NA)	NA (12.68 to NA)

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

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

Time frame:: From the date of first dose up to first documentation of disease progression or death (up to 3 years and 7.5 months)
Reported as:: Median · Months

Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria
Months	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria	3.12 (2.79 to 3.29)	8.94 (3.78 to 11.56)	2.56 (2.14 to NA)	4.44 (3.29 to 6.24)	5.75 (2.37 to 6.47)	1.81 (0.82 to 3.48)	2.66 (0.66 to 7.39)	1.87 (1.48 to 1.91)

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

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

Time frame:: From the date of first dose up to the date of death (up to 3 years and 7.5 months)
Reported as:: Median · Months

Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)
Months	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)	14.46 (13.93 to 14.98)	13.44 (4.14 to 20.24)	10.25 (4.44 to 19.84)	12.71 (9.79 to 14.46)	14.23 (7.98 to NA)	6.00 (2.60 to 9.79)	8.62 (2.96 to NA)	7.79 (6.21 to 10.68)

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

Time frame:: From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)
Reported as:: Number · Number of participants

Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Number of participants	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm C: E- Pamiparib + Temozolomide 60 mg
Participants with at Lease 1 TEAE	40	29
TEAE with Grade 3 or Higher	25	19
Treatment Emergent SAEs	18	11
TEAE Leading to Death	3	1

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

Time frame:: From the date of first dose up to EOS visit (up to 3 years and 7.5 months)
Reported as:: Number · Number of participants

Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Number of participants	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm C: E- Pamiparib + Temozolomide 60 mg
Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements	0	0

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

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

Time frame:: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
Reported as:: Number · participants

Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants
participants	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm C: E- Pamiparib + Temozolomide 60 mg
<1 cycle	3	8
1 cycle	9	8
2 cycles	2	7
3 cycles	2	1
4 cycles	3	1
5 cycles	3	0
6 cycles	3	0
7 cycles	0.0	0
>7 cycles	4	5

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

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

Time frame:: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
Reported as:: Mean · Milligrams/Day

Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant
Milligrams/Day	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm C: E- Pamiparib + Temozolomide 60 mg
Pamiparib	109.0 ± 22.07	109.5 ± 15.22
TMZ	NA ± NA	19.6 ± 11.60

Adverse events

Collected over From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months). Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	2/3 (66.7%)	0/3 (0%)	3/3 (100%)
Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	7/8 (87.5%)	2/8 (25%)	8/8 (100%)
Arm A: DE- Pamiparib 6Wks + RT 6 Wks	8/9 (88.9%)	2/9 (22.2%)	9/9 (100%)
Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	27/40 (67.5%)	18/40 (45%)	40/40 (100%)
Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	4/9 (44.4%)	2/9 (22.2%)	9/9 (100%)
Arm C: DE - Pamiparib + Temozolomide 20 mg	8/9 (88.9%)	4/9 (44.4%)	9/9 (100%)
Arm C: DE - Pamiparib + Temozolomide 40 mg	6/8 (75%)	3/8 (37.5%)	7/8 (87.5%)
Arm C: E- Pamiparib + Temozolomide 60 mg	21/30 (70%)	11/30 (36.7%)	29/30 (96.7%)

Most frequent serious events

Showing 10 of 55

Most frequent serious events
Event	Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
Gastrointestinal haemorrhageGastrointestinal disorders	0/3	1/8	0/9	0/40	0/9	0/9	0/8	0/30
NauseaGastrointestinal disorders	0/3	0/8	1/9	1/40	0/9	0/9	1/8	0/30
VomitingGastrointestinal disorders	0/3	0/8	1/9	1/40	0/9	0/9	1/8	0/30
FatigueGeneral disorders	0/3	0/8	0/9	2/40	0/9	0/9	1/8	0/30
Vasogenic cerebral oedemaNervous system disorders	0/3	1/8	0/9	1/40	0/9	0/9	1/8	0/30
Confusional statePsychiatric disorders	0/3	0/8	0/9	0/40	0/9	0/9	1/8	1/30
Pulmonary embolismRespiratory, thoracic and mediastinal disorders	0/3	0/8	0/9	3/40	0/9	0/9	1/8	0/30
Deep vein thrombosisVascular disorders	0/3	0/8	0/9	0/40	0/9	0/9	1/8	0/30
AnaemiaBlood and lymphatic system disorders	0/3	0/8	0/9	2/40	1/9	0/9	0/8	0/30
Febrile neutropeniaBlood and lymphatic system disorders	0/3	0/8	0/9	0/40	1/9	0/9	0/8	0/30

Most frequent other events

Showing 10 of 211

Most frequent other events
Event	Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg
FatigueGeneral disorders	3/3	2/8	6/9	29/40	6/9	1/9	4/8	17/30
NauseaGastrointestinal disorders	1/3	3/8	5/9	29/40	7/9	4/9	4/8	13/30
AlopeciaSkin and subcutaneous tissue disorders	2/3	2/8	2/9	14/40	4/9	0/9	0/8	0/30
VomitingGastrointestinal disorders	1/3	0/8	2/9	13/40	2/9	1/9	4/8	7/30
HeadacheNervous system disorders	1/3	1/8	4/9	18/40	2/9	1/9	0/8	8/30
AnaemiaBlood and lymphatic system disorders	0/3	1/8	0/9	13/40	4/9	3/9	3/8	6/30
White blood cell count decreasedInvestigations	0/3	0/8	1/9	6/40	4/9	2/9	1/8	6/30
Decreased appetiteMetabolism and nutrition disorders	1/3	1/8	3/9	14/40	4/9	2/9	1/8	7/30
ConstipationGastrointestinal disorders	0/3	1/8	3/9	14/40	3/9	2/9	2/8	12/30
FallInjury, poisoning and procedural complications	0/3	1/8	0/9	5/40	1/9	0/9	3/8	5/30

Baseline characteristics

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.

Age, Continuous
Age, Continuous(years)	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg	Total
Mean	59.7 ± 8.39	63.4 ± 8.80	58.8 ± 7.66	56.7 ± 13.48	60.9 ± 9.94	49.2 ± 12.63	49.1 ± 15.51	58.6 ± 10.54	57.10 ± 12.10

Sex: Female, Male
Sex: Female, Male(Participants)	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg	Total
Female	0	1	2	17	4	1	4	10	39
Male	3	7	7	23	5	8	4	20	77

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks	Arm A: DE-Pamiparib 4 Wks + RT 6 Wks	Arm A: DE- Pamiparib 6Wks + RT 6 Wks	Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks	Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide	Arm C: DE - Pamiparib + Temozolomide 20 mg	Arm C: DE - Pamiparib + Temozolomide 40 mg	Arm C: E- Pamiparib + Temozolomide 60 mg	Total
Asian	0	0	1	0	0	0	0	1	2
Black or African American	0	1	1	0	0	1	0	0	3
White	3	7	7	38	9	7	8	27	106
Unknown/Not Reported	0	0	0	2	0	1	0	2	5

Study locations

22 sites

Center For Neurosciences
Tucson, Arizona 85718, United States
UCLA
Los Angeles, California 90095, United States
University of California At San Francisco
San Francisco, California 94143, United States
Sarah Cannon Research Institute (Scri) At Health One
Denver, Colorado 80219, United States
Massachusetts General Hospital
Boston, Massachusetts 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts 02215, United States
Henry Ford Hospital
Detroit, Michigan 48202, United States
Midamerica Division, Inc
Kansas City, Missouri 64132, United States
Washington University in St Louis
Saint Louis, Missouri 63110, United States
Memorial Sloan Kettering Cancer Center Mskcc
New York, New York 10065, United States
Cleveland Clinic Foundation
Cleveland, Ohio 44195, United States
Ohio State University
Columbus, Ohio 43210, United States
Sarah Cannon Research Institute (Scri) Stephenson Cancer Center
Oklahoma City, Oklahoma 73104, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania 17033, United States
Thomas Jefferson University Hospital Jefferson Health
Philadelphia, Pennsylvania 19107, United States
Tennessee Oncology, Pllc Nashville
Nashville, Tennessee 37203, United States
Huntsman Cancer Institute
Salt Lake City, Utah 84112, United States
University of Virginia
Charlottesville, Virginia 22903, United States
Liverpool Hospital
Liverpool, New South Wales 2170, Australia
Institut Gustave Roussy
Villejuif, 94805, France
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
University of Zurich Medical School
Zurich, 8032, Switzerland

References and documents

Publications

Xiong Y, Guo Y, Liu Y, Wang H, Gong W, Liu Y, Wang X, Gao Y, Yu F, Su D, Wang F, Zhu Y, Zhao Y, Wu Y, Qin Z, Sun X, Ren B, Jiang B, Jin W, Shen Z, Tang Z, Song X, Wang L, Liu X, Zhou C, Jiang B. Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor. Neoplasia. 2020 Sep;22(9):431-440. doi: 10.1016/j.neo.2020.06.009. Epub 2020 Jul 8. PubMed 32652442 ↗

Study documents

Study protocol · Jul 23, 2018
Statistical analysis plan · Apr 20, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 4, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03150862
Lead sponsor: BeiGene USA, Inc.
Responsible party: Sponsor
First posted: May 12, 2017
Start date: Jul 24, 2017
Primary completion: Mar 17, 2021
Completion: Mar 17, 2021
Results posted: May 31, 2022
Last update: Feb 4, 2025

Study contacts

Study Director

study director · BeiGene

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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