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

Sponsor
BeiGene USA, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03150862
Collaborator
(none)
116
Enrollment
20
Locations
5
Arms
43.8
Actual Duration (Months)
5.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
116 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
No Masking
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jul 24, 2017
Actual Primary Completion Date :
Mar 17, 2021
Actual Study Completion Date :
Mar 17, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (Dose Escalation)

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

Drug: Pamiparib
Administered as specified in the treatment arm
Other Names:
  • BGB-290

    • Radiation: Radiation
    Up to 60 Gy (total) over 6 - 7 weeks
    Experimental: Arm B (Dose Escalation)

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

    Drug: Pamiparib
    Administered as specified in the treatment arm
    Other Names:
  • BGB-290

    • Drug: TMZ
    Administered as specified in the treatment arm

    Radiation: Radiation
    Up to 60 Gy (total) over 6 - 7 weeks
    Experimental: Arm A (Dose Expansion)

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

    Drug: Pamiparib
    Administered as specified in the treatment arm
    Other Names:
  • BGB-290

    • Radiation: Radiation
    Up to 60 Gy (total) over 6 - 7 weeks
    Experimental: Arm C (Dose Escalation)

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

    Drug: Pamiparib
    Administered as specified in the treatment arm
    Other Names:
  • BGB-290

    • Drug: TMZ
    Administered as specified in the treatment arm
    Experimental: Arm C (Dose Expansion-Cohorts C1 and C2)

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

    Drug: Pamiparib
    Administered as specified in the treatment arm
    Other Names:
  • BGB-290

    • Drug: TMZ
    Administered as specified in the treatment arm

    Outcome Measures

    Primary Outcome Measures

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

      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)

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

      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.

    3. Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements [From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)]

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

      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.

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

      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).

    6. Phase 1b Arm C: Number of Cycles of Treatment Received by Participants [From the date of first dose up to EOS visit ( up to 3 years and 7.5 months)]

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

    7. Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant [From the date of first dose until EOS visit (up to 3 years and 7.5 months)]

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

    Secondary Outcome Measures

    1. Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib [Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy]

    2. Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria [From the date of first dose up to first documentation of disease progression while participant is alive (approximately 3 years and 7.5 months)]

      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.

    3. Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria [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)]

      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

    4. Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria [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)]

      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).

    5. Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria [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)]

      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).

    6. Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria [From first documentation of CR or PR to first documentation of disease progression or death (up to 3 years and 7.5 months)]

      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).

    7. Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria [From the date of first dose up to first documentation of disease progression or death (up to 3 years and 7.5 months)]

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

    8. Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS) [From the date of first dose up to the date of death (up to 3 years and 7.5 months)]

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

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

      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.

    10. Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements [From the date of first dose up to EOS visit (up to 3 years and 7.5 months)]

    11. Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants [From date of first dose up to EOS Visit (up to 3 years and 7.5 months)]

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

    12. Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant [From date of first dose up to EOS Visit (up to 3 years and 7.5 months)]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Key Inclusion Criteria: All participants

    1. Age ≥ 18 years old.

    2. Confirmed diagnosis of glioblastoma (WHO Grade IV).

    3. Agreement to provide archival tumor tissue for exploratory biomarker analysis

    4. Ability to undergo serial MRIs.

    5. Eastern Cooperative Oncology Group (ECOG) status ≤ 1.

    6. Adequate hematologic and end-organ function

    7. 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.

    8. Ability to swallow whole capsules.

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

    1. No previous treatment for GBM except surgery.

    2. 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.

    3. Documented unmethylated MGMT promoter status.

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

    1. Documentation of MGMT promoter status

    2. No prior systemic chemotherapy other than TMZ for GBM.

    3. Histologically confirmed secondary glioblastoma

    4. 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:

    1. Histologically confirmed de novo (primary) glioblastoma with unequivocal first progressive disease (PD) after RT with concurrent/adjuvant TMZ chemotherapy

    2. Disease that is measurable as defined by RANO criteria

    3. Documentation of MGMT promoter status

    Key Exclusion Criteria: All participants

    1. Prior chemotherapy, biologic therapy, immunotherapy or investigational agents ≤21 days prior to start of study treatment.

    2. Toxicity of ≥ Grade 2 from prior therapy.

    3. Major surgery or significant other injury ≤ 4 weeks prior to start of study treatment.

    4. 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.

    5. Active infection requiring systemic treatment.

    6. Known human immunodeficiency virus (HIV) or active viral hepatitis.

    7. 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.

    8. Active clinically significant gastrointestinal disease.

    9. Active bleeding disorder ≤ 6 months prior to start of treatment.

    10. Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants.

    11. Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.

    12. Pregnant or nursing females.

    13. Significant intercurrent illness that may result in participant's death prior to death from glioblastoma.

    Arms B and C Only:

    1. Known hypersensitivity to any component of TMZ or decarbazine (DTIC).

    2. Have hereditary problems of galactose intolerance

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Center for Neurosciences Tucson Arizona United States 85718
    2 UCLA Neuro-Oncology Los Angeles California United States 90095
    3 University of California at San Francisco San Francisco California United States 94143
    4 Sarah Cannon Research Institute at Health One Denver Colorado United States 80218
    5 Massachusetts General Hospital Pappas Center for Neuro-Oncology Boston Massachusetts United States 02214
    6 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    7 Henry Ford Health Systems Detroit Michigan United States 48202
    8 Health Midwest Ventures Group, LLC Kansas City Missouri United States 64132
    9 Washington University Saint Louis Missouri United States 63110
    10 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    11 Cleveland Clinic Cleveland Ohio United States 44195
    12 The Ohio State University Columbus Ohio United States 43210
    13 University of Oklahoma Health Sciences Center (Stephenson Cancer Center) Oklahoma City Oklahoma United States 73104
    14 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033
    15 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    16 SCRI / Tennessee Oncology Nashville Tennessee United States 37203
    17 Huntsman Cancer Center Salt Lake City Utah United States 84112
    18 University of Virginia Health Systems Charlottesville Virginia United States 22903
    19 Erasmus University Medical Center Rotterdam Netherlands 3015 GD
    20 Universitätsspital Zuerich - Klinik fur Neurologie Zurich Switzerland CH-8091

    Sponsors and Collaborators

    • BeiGene USA, Inc.

    Investigators

    • Study Director: Study Director, BeiGene

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    BeiGene USA, Inc.
    ClinicalTrials.gov Identifier:
    NCT03150862
    Other Study ID Numbers:
    • BGB-290-104
    • 2017-001554-33
    First Posted:
    May 12, 2017
    Last Update Posted:
    May 31, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by BeiGene USA, Inc.
    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
    Additional relevant MeSH terms:
    Glioblastoma
    Nervous System Neoplasms
    Central Nervous System Neoplasms

    Study Results

    Participant Flow

    Recruitment Details 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.
    Pre-assignment Detail
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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
    Period Title: Overall Study
    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

    Baseline Characteristics

    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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 Total of all reporting groups
    Overall Participants 3 8 9 40 9 9 8 30 116
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    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 (Count of Participants)
    Female
    0
    0%
    1
    12.5%
    2
    22.2%
    17
    42.5%
    4
    44.4%
    1
    11.1%
    4
    50%
    10
    33.3%
    39
    33.6%
    Male
    3
    100%
    7
    87.5%
    7
    77.8%
    23
    57.5%
    5
    55.6%
    8
    88.9%
    4
    50%
    20
    66.7%
    77
    66.4%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3.3%
    2
    1.7%
    Black or African American
    0
    0%
    1
    12.5%
    1
    11.1%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    3
    2.6%
    White
    3
    100%
    7
    87.5%
    7
    77.8%
    38
    95%
    9
    100%
    7
    77.8%
    8
    100%
    27
    90%
    106
    91.4%
    Unknown/Not Reported
    0
    0%
    0
    0%
    0
    0%
    2
    5%
    0
    0%
    1
    11.1%
    0
    0%
    2
    6.7%
    5
    4.3%

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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
    Measure Participants 3 8 9 9 9 8
    Number [participants]
    0
    0%
    0
    0%
    2
    22.2%
    1
    2.5%
    0
    0%
    3
    33.3%
    2. Primary Outcome
    Title Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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
    Measure Participants 3 8 9 9 9 8
    Participants with At Least 1 TEAE
    3
    100%
    8
    100%
    9
    100%
    9
    22.5%
    9
    100%
    8
    88.9%
    TEAE with Grade 3 or Higher
    1
    33.3%
    3
    37.5%
    4
    44.4%
    4
    10%
    5
    55.6%
    7
    77.8%
    Treatment Emergent SAEs
    0
    0%
    2
    25%
    2
    22.2%
    2
    5%
    4
    44.4%
    3
    33.3%
    TEAE Leading to Death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3. Primary Outcome
    Title Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
    Description
    Time Frame From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
    Arm/Group Description 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 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
    Measure Participants 9 8
    Number [Number of participants]
    0
    0%
    0
    0%
    4. Primary Outcome
    Title Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks
    Arm/Group Description 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
    Measure Participants 32
    Number (95% Confidence Interval) [Percentage of participants]
    65.6
    2186.7%
    5. Primary Outcome
    Title Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm C: E- Pamiparib + Temozolomide 60 mg
    Arm/Group Description 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
    Measure Participants 28
    Number (95% Confidence Interval) [Percentage of participants]
    10.7
    356.7%
    6. Primary Outcome
    Title Phase 1b Arm C: Number of Cycles of Treatment Received by Participants
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
    Arm/Group Description 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 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
    Measure Participants 9 8
    <1 cycle
    2
    66.7%
    3
    37.5%
    1 cycle
    4
    133.3%
    0
    0%
    2 cycles
    1
    33.3%
    2
    25%
    3 cycles
    0
    0%
    1
    12.5%
    4 cycles
    1
    33.3%
    0
    0%
    5 cycles
    1
    33.3%
    0
    0%
    6 cycles
    0
    0%
    0
    0%
    7 cycles
    0
    0%
    0
    0%
    >7 cycles
    0
    0%
    2
    25%
    7. Primary Outcome
    Title Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
    Arm/Group Description 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 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
    Measure Participants 9 8
    Pamiparib
    97.5
    (25.41)
    107.6
    (14.65)
    TMZ
    13.6
    (1.88)
    28.2
    (10.80)
    8. Secondary Outcome
    Title Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib
    Description
    Time Frame Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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
    Measure Participants 3 5 6 35 7 6 6 25
    Mean (Standard Deviation) [ng/mL]
    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)
    9. Secondary Outcome
    Title Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Efficacy Analysis Set; Participants with available data were included in the analysis
    Arm/Group Title 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/Group Description 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 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 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 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
    Measure Participants 3 6 7 5
    Number (95% Confidence Interval) [Percentage of participants]
    66.7
    2223.3%
    100.0
    1250%
    42.9
    476.7%
    80.0
    200%
    10. Secondary Outcome
    Title Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Efficacy Analysis Set; Participants with available data were included in the analysis.
    Arm/Group Title Arm C: DE- Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
    Arm/Group Description 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 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
    Measure Participants 9 7
    Number (95% Confidence Interval) [Percentage of participants]
    55.6
    1853.3%
    71.4
    892.5%
    11. Secondary Outcome
    Title Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Analysis Set; Participants with available data were included in the analysis.
    Arm/Group Title 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/Group Description 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 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 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 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 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
    Measure Participants 3 6 7 32 5
    Number (95% Confidence Interval) [Percentage of participants]
    0
    0%
    16.7
    208.8%
    0
    0%
    3.1
    7.8%
    0
    0%
    12. Secondary Outcome
    Title Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Efficacy Analysis Set; participants with available data were included in the analysis
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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
    Measure Participants 3 6 7 32 5 9 7 28
    Number (95% Confidence Interval) [Percentage of participants]
    0
    0%
    33.3
    416.3%
    0
    0%
    37.6
    94%
    40.0
    444.4%
    0
    0%
    28.6
    357.5%
    17.9
    59.7%
    13. Secondary Outcome
    Title Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Efficacy Analysis Set; Only the participants with objective responses were included in DOR analysis.
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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
    Measure Participants 0 1 0 1 0 0 1 3
    Median (95% Confidence Interval) [Months]
    6.44
    10.32
    11.7
    NA
    14. Secondary Outcome
    Title Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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
    Measure Participants 3 8 9 40 8 9 8 30
    Median (95% Confidence Interval) [Months]
    3.12
    8.94
    2.56
    4.44
    5.75
    1.81
    2.66
    1.87
    15. Secondary Outcome
    Title Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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
    Measure Participants 3 8 9 40 8 9 8 30
    Median (95% Confidence Interval) [Months]
    14.46
    13.44
    10.25
    12.71
    14.23
    6.00
    8.62
    7.79
    16. Secondary Outcome
    Title Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
    Arm/Group Description 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 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
    Measure Participants 40 30
    Participants with at Lease 1 TEAE
    40
    1333.3%
    29
    362.5%
    TEAE with Grade 3 or Higher
    25
    833.3%
    19
    237.5%
    Treatment Emergent SAEs
    18
    600%
    11
    137.5%
    TEAE Leading to Death
    3
    100%
    1
    12.5%
    17. Secondary Outcome
    Title Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
    Description
    Time Frame From the date of first dose up to EOS visit (up to 3 years and 7.5 months)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
    Arm/Group Description 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 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
    Measure Participants 40 30
    Number [Number of participants]
    0
    0%
    0
    0%
    18. Secondary Outcome
    Title Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set; For Arm A Only participants who entered the maintenance phase were included in the analysis as per protocol.
    Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
    Arm/Group Description 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 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
    Measure Participants 29 30
    <1 cycle
    3
    100%
    8
    100%
    1 cycle
    9
    300%
    8
    100%
    2 cycles
    2
    66.7%
    7
    87.5%
    3 cycles
    2
    66.7%
    1
    12.5%
    4 cycles
    3
    100%
    1
    12.5%
    5 cycles
    3
    100%
    0
    0%
    6 cycles
    3
    100%
    0
    0%
    7 cycles
    0.0
    0%
    0
    0%
    >7 cycles
    4
    133.3%
    5
    62.5%
    19. Secondary Outcome
    Title Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
    Arm/Group Description 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 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
    Measure Participants 40 30
    Pamiparib
    109.0
    (22.07)
    109.5
    (15.22)
    TMZ
    NA
    (NA)
    19.6
    (11.60)

    Adverse Events

    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)
    Adverse Event Reporting Description 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.
    Arm/Group Title 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
    Arm/Group Description 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 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 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 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 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 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 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 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
    All Cause Mortality
    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
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 7/8 (87.5%) 8/9 (88.9%) 27/40 (67.5%) 4/9 (44.4%) 8/9 (88.9%) 6/8 (75%) 21/30 (70%)
    Serious Adverse Events
    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
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 2/8 (25%) 2/9 (22.2%) 18/40 (45%) 2/9 (22.2%) 4/9 (44.4%) 3/8 (37.5%) 11/30 (36.7%)
    Blood and lymphatic system disorders
    Anaemia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Febrile neutropenia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Neutropenia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Ear and labyrinth disorders
    Vertigo 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Gastrointestinal disorders
    Anal incontinence 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Constipation 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Gastrointestinal haemorrhage 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Nausea 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 1/40 (2.5%) 2 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Vomiting 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 1/40 (2.5%) 2 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    General disorders
    Asthenia 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Chills 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Fatigue 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Gait disturbance 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Impaired healing 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Pyrexia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Infections and infestations
    Bronchitis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Pneumonia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Sepsis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Wound infection 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Subarachnoid haematoma 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Musculoskeletal and connective tissue disorders
    Muscular weakness 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 2/30 (6.7%) 2
    Neck pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Tumour flare 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Nervous system disorders
    Aphasia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 1/30 (3.3%) 1
    Apraxia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Brain oedema 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Cerebral cyst 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Cerebrovascular accident 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Depressed level of consciousness 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Dysaesthesia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Dysarthria 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Hemiparesis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Hemiplegia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Hydrocephalus 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Nervous system disorder 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Partial seizures 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Psychogenic seizure 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Seizure 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 1/9 (11.1%) 1 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Syncope 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Vasogenic cerebral oedema 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Psychiatric disorders
    Agitation 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Confusional state 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 1/30 (3.3%) 1
    Mental status changes 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Suicide attempt 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Laryngeal haemorrhage 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Pulmonary embolism 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 3 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Vascular disorders
    Deep vein thrombosis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Embolism 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Haematoma 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Hypotension 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Other (Not Including Serious) Adverse Events
    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
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 8/8 (100%) 9/9 (100%) 40/40 (100%) 9/9 (100%) 9/9 (100%) 7/8 (87.5%) 29/30 (96.7%)
    Blood and lymphatic system disorders
    Anaemia 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 13/40 (32.5%) 19 4/9 (44.4%) 7 3/9 (33.3%) 3 3/8 (37.5%) 6 6/30 (20%) 15
    Increased tendency to bruise 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Leukopenia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Lymphopenia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 4/30 (13.3%) 4
    Neutropenia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 3 1/9 (11.1%) 2 0/9 (0%) 0 1/8 (12.5%) 1 3/30 (10%) 3
    Thrombocytopenia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 4/40 (10%) 5 1/9 (11.1%) 1 0/9 (0%) 0 1/8 (12.5%) 2 3/30 (10%) 3
    Cardiac disorders
    Angina pectoris 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Bradycardia 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Sinus tachycardia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Tachycardia 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 1/30 (3.3%) 1
    Ventricular extrasystoles 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Ear and labyrinth disorders
    Ear congestion 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Ear discomfort 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Ear pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Hypoacusis 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Tinnitus 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 3 1/9 (11.1%) 1 0/9 (0%) 0 1/8 (12.5%) 1 1/30 (3.3%) 1
    Vertigo 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 2 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Eye disorders
    Dry eye 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Erythema of eyelid 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Lacrimation increased 0/3 (0%) 0 1/8 (12.5%) 1 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Photophobia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Vision blurred 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 3/40 (7.5%) 3 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Visual impairment 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Gastrointestinal disorders
    Abdominal discomfort 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Abdominal distension 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Abdominal pain 1/3 (33.3%) 1 1/8 (12.5%) 1 1/9 (11.1%) 1 5/40 (12.5%) 8 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Breath odour 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Colitis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Constipation 0/3 (0%) 0 1/8 (12.5%) 1 3/9 (33.3%) 3 14/40 (35%) 16 3/9 (33.3%) 3 2/9 (22.2%) 2 2/8 (25%) 2 12/30 (40%) 17
    Diarrhoea 0/3 (0%) 0 2/8 (25%) 2 0/9 (0%) 0 12/40 (30%) 17 2/9 (22.2%) 2 2/9 (22.2%) 2 1/8 (12.5%) 1 4/30 (13.3%) 5
    Dry mouth 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 4/40 (10%) 4 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Dyspepsia 0/3 (0%) 0 1/8 (12.5%) 1 1/9 (11.1%) 1 2/40 (5%) 2 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Dysphagia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Eructation 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Femoral hernia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Flatulence 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Gastrooesophageal reflux disease 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 1/30 (3.3%) 1
    Haematemesis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Hyperaesthesia teeth 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Inguinal hernia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 2
    Melaena 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Nausea 1/3 (33.3%) 1 3/8 (37.5%) 3 5/9 (55.6%) 5 29/40 (72.5%) 42 7/9 (77.8%) 8 4/9 (44.4%) 4 4/8 (50%) 5 13/30 (43.3%) 18
    Oral dysaesthesia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Retching 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Stomatitis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Tooth discolouration 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Umbilical hernia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Vomiting 1/3 (33.3%) 1 0/8 (0%) 0 2/9 (22.2%) 2 13/40 (32.5%) 20 2/9 (22.2%) 2 1/9 (11.1%) 1 4/8 (50%) 5 7/30 (23.3%) 15
    Vomiting projectile 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    General disorders
    Asthenia 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 2
    Chest pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Chills 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Early satiety 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Fatigue 3/3 (100%) 3 2/8 (25%) 2 6/9 (66.7%) 7 29/40 (72.5%) 34 6/9 (66.7%) 7 1/9 (11.1%) 1 4/8 (50%) 4 17/30 (56.7%) 20
    Feeling cold 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Gait disturbance 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 2/9 (22.2%) 2 1/9 (11.1%) 1 1/8 (12.5%) 1 2/30 (6.7%) 2
    Influenza like illness 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 1/30 (3.3%) 1
    Malaise 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 3 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 2
    Non-cardiac chest pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Oedema peripheral 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 4/40 (10%) 4 2/9 (22.2%) 2 1/9 (11.1%) 1 0/8 (0%) 0 3/30 (10%) 4
    Pyrexia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 3/30 (10%) 3
    Swelling face 0/3 (0%) 0 1/8 (12.5%) 2 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Vessel puncture site pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Hepatobiliary disorders
    Hepatic lesion 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 2
    Infections and infestations
    Cellulitis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Eye infection 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Hordeolum 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Influenza 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Oral candidiasis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 2/9 (22.2%) 2 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 2
    Oral herpes 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 3
    Osteomyelitis chronic 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Otitis media 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Pneumonia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Postoperative wound infection 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Sinusitis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Tooth infection 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Upper respiratory tract infection 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 3 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Urinary tract infection 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 1/40 (2.5%) 2 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Wound infection 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Injury, poisoning and procedural complications
    Contusion 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 3 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 3/30 (10%) 3
    Eye contusion 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Fall 0/3 (0%) 0 1/8 (12.5%) 2 0/9 (0%) 0 5/40 (12.5%) 6 1/9 (11.1%) 1 0/9 (0%) 0 3/8 (37.5%) 3 5/30 (16.7%) 8
    Ligament sprain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Pseudomeningocele 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Radiation injury 0/3 (0%) 0 1/8 (12.5%) 2 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Radiation skin injury 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Skin laceration 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 3
    Subdural haematoma 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Traumatic haematoma 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 3 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 1/30 (3.3%) 1
    Aspartate aminotransferase increased 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 3 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Blood bilirubin increased 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 4 1/9 (11.1%) 1 2/9 (22.2%) 2 1/8 (12.5%) 1 1/30 (3.3%) 1
    Blood bilirubin unconjugated increased 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Blood creatinine increased 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 4/40 (10%) 5 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 2/30 (6.7%) 3
    Cortisol decreased 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Electrocardiogram QT prolonged 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Lymphocyte count decreased 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 3/40 (7.5%) 3 2/9 (22.2%) 2 3/9 (33.3%) 3 1/8 (12.5%) 1 4/30 (13.3%) 5
    Neutrophil count decreased 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 6/40 (15%) 9 3/9 (33.3%) 3 2/9 (22.2%) 2 2/8 (25%) 2 5/30 (16.7%) 10
    Platelet count decreased 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 7/40 (17.5%) 8 1/9 (11.1%) 2 3/9 (33.3%) 3 1/8 (12.5%) 1 8/30 (26.7%) 18
    Weight decreased 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 9/40 (22.5%) 10 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 3/30 (10%) 3
    White blood cell count decreased 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 6/40 (15%) 8 4/9 (44.4%) 7 2/9 (22.2%) 2 1/8 (12.5%) 1 6/30 (20%) 10
    Metabolism and nutrition disorders
    Decreased appetite 1/3 (33.3%) 1 1/8 (12.5%) 1 3/9 (33.3%) 3 14/40 (35%) 15 4/9 (44.4%) 4 2/9 (22.2%) 2 1/8 (12.5%) 1 7/30 (23.3%) 8
    Dehydration 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 1/40 (2.5%) 2 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Hyperglycaemia 1/3 (33.3%) 1 0/8 (0%) 0 1/9 (11.1%) 1 2/40 (5%) 3 1/9 (11.1%) 1 2/9 (22.2%) 2 0/8 (0%) 0 1/30 (3.3%) 1
    Hypernatraemia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 1 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Hypoalbuminaemia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Hypocalcaemia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Hypokalaemia 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 2/40 (5%) 2 2/9 (22.2%) 2 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Hyponatraemia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 4/40 (10%) 7 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 1/30 (3.3%) 1
    Hypophosphataemia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 4 0/9 (0%) 0 1/9 (11.1%) 1 1/8 (12.5%) 1 0/30 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 2/9 (22.2%) 2 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Back pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 3 1/9 (11.1%) 1 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Flank pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Groin pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Muscle spasms 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 2 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Muscular weakness 0/3 (0%) 0 1/8 (12.5%) 1 1/9 (11.1%) 1 1/40 (2.5%) 1 1/9 (11.1%) 1 1/9 (11.1%) 1 1/8 (12.5%) 1 3/30 (10%) 3
    Musculoskeletal pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 3
    Myalgia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 3/30 (10%) 3
    Neck pain 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Pain in extremity 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Pain in jaw 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Tenosynovitis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal hamartoma 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Nervous system disorders
    Ageusia 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Amnesia 1/3 (33.3%) 1 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Aphasia 0/3 (0%) 0 1/8 (12.5%) 1 3/9 (33.3%) 3 6/40 (15%) 7 1/9 (11.1%) 2 1/9 (11.1%) 1 0/8 (0%) 0 3/30 (10%) 3
    Ataxia 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Balance disorder 0/3 (0%) 0 0/8 (0%) 0 2/9 (22.2%) 2 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Brain oedema 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 0/30 (0%) 0
    Carpal tunnel syndrome 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Cerebrospinal fluid leakage 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Cognitive disorder 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 2/9 (22.2%) 2 0/8 (0%) 0 0/30 (0%) 0
    Disturbance in attention 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 1/30 (3.3%) 1
    Dizziness 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 11/40 (27.5%) 12 2/9 (22.2%) 2 1/9 (11.1%) 1 1/8 (12.5%) 1 8/30 (26.7%) 8
    Drooling 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Dysaesthesia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Dysarthria 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Dysgeusia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 10/40 (25%) 11 2/9 (22.2%) 2 1/9 (11.1%) 1 0/8 (0%) 0 2/30 (6.7%) 3
    Dyslexia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Encephalopathy 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Epilepsy 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 3
    Facial paralysis 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Facial paresis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 1/30 (3.3%) 1
    Headache 1/3 (33.3%) 1 1/8 (12.5%) 1 4/9 (44.4%) 4 18/40 (45%) 24 2/9 (22.2%) 3 1/9 (11.1%) 1 0/8 (0%) 0 8/30 (26.7%) 11
    Hemianopia homonymous 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Hemiparesis 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 8/40 (20%) 9 3/9 (33.3%) 3 3/9 (33.3%) 3 1/8 (12.5%) 1 4/30 (13.3%) 4
    Hypersomnia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Hypoaesthesia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Memory impairment 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 6/40 (15%) 6 1/9 (11.1%) 1 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Muscle spasticity 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 2
    Myoclonus 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Paraesthesia 0/3 (0%) 0 1/8 (12.5%) 1 1/9 (11.1%) 1 1/40 (2.5%) 1 1/9 (11.1%) 1 1/9 (11.1%) 1 0/8 (0%) 0 2/30 (6.7%) 2
    Partial seizures 0/3 (0%) 0 1/8 (12.5%) 1 1/9 (11.1%) 1 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Peripheral motor neuropathy 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 2 0/8 (0%) 0 0/30 (0%) 0
    Peripheral sensory neuropathy 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Seizure 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 6/40 (15%) 9 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 4/30 (13.3%) 4
    Somnolence 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Taste disorder 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Tremor 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 2 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Visual field defect 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 3/40 (7.5%) 3 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 2/30 (6.7%) 2
    Psychiatric disorders
    Agitation 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 4/40 (10%) 4 1/9 (11.1%) 1 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Alcohol abuse 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Anxiety 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 6/40 (15%) 6 2/9 (22.2%) 2 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Confusional state 0/3 (0%) 0 2/8 (25%) 2 1/9 (11.1%) 1 4/40 (10%) 5 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 3/30 (10%) 3
    Decreased interest 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Depression 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 3/30 (10%) 3
    Insomnia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 6/40 (15%) 6 2/9 (22.2%) 2 0/9 (0%) 0 1/8 (12.5%) 1 4/30 (13.3%) 4
    Irritability 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Persistent depressive disorder 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Suicidal ideation 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Renal and urinary disorders
    Acute kidney injury 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Haematuria 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Nephrolithiasis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Pollakiuria 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 1/8 (12.5%) 1 1/30 (3.3%) 1
    Polyuria 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Urinary incontinence 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 6/40 (15%) 6 2/9 (22.2%) 2 1/9 (11.1%) 1 0/8 (0%) 0 0/30 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Cough 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 4/40 (10%) 5 0/9 (0%) 0 1/9 (11.1%) 1 0/8 (0%) 0 2/30 (6.7%) 3
    Dysphonia 0/3 (0%) 0 2/8 (25%) 2 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Dyspnoea 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 4/30 (13.3%) 5
    Dyspnoea exertional 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Epistaxis 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Hiccups 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Hypoxia 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 1/9 (11.1%) 2 0/8 (0%) 0 0/30 (0%) 0
    Laryngeal inflammation 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Nasal congestion 0/3 (0%) 0 1/8 (12.5%) 1 1/9 (11.1%) 1 3/40 (7.5%) 3 1/9 (11.1%) 1 0/9 (0%) 0 1/8 (12.5%) 1 3/30 (10%) 3
    Nasal polyps 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Productive cough 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Pulmonary embolism 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Rhinitis allergic 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Sinus congestion 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Upper-airway cough syndrome 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Wheezing 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Skin and subcutaneous tissue disorders
    Acne 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Alopecia 2/3 (66.7%) 2 2/8 (25%) 2 2/9 (22.2%) 2 14/40 (35%) 16 4/9 (44.4%) 4 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Dermatitis 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Dermatitis acneiform 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Dermatitis contact 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Dry skin 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Erythema 0/3 (0%) 0 1/8 (12.5%) 1 1/9 (11.1%) 1 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Night sweats 0/3 (0%) 0 1/8 (12.5%) 1 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Pain of skin 0/3 (0%) 0 2/8 (25%) 2 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Petechiae 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Pruritus 1/3 (33.3%) 1 1/8 (12.5%) 1 0/9 (0%) 0 1/40 (2.5%) 1 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Purpura 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Rash maculo-papular 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 3/9 (33.3%) 3 2/9 (22.2%) 2 0/8 (0%) 0 2/30 (6.7%) 2
    Skin atrophy 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 2/40 (5%) 2 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Vascular disorders
    Deep vein thrombosis 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 1/40 (2.5%) 1 1/9 (11.1%) 1 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1
    Hypertension 0/3 (0%) 0 0/8 (0%) 0 1/9 (11.1%) 1 1/40 (2.5%) 1 2/9 (22.2%) 2 0/9 (0%) 0 0/8 (0%) 0 0/30 (0%) 0
    Hypotension 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 1/9 (11.1%) 1 1/9 (11.1%) 1 0/8 (0%) 0 1/30 (3.3%) 1
    Pallor 0/3 (0%) 0 0/8 (0%) 0 0/9 (0%) 0 0/40 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/8 (0%) 0 1/30 (3.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.

    Results Point of Contact

    Name/Title Study Director
    Organization BeiGene
    Phone +1-877-828-5568
    Email clinicaltrials@beigene.com
    Responsible Party:
    BeiGene USA, Inc.
    ClinicalTrials.gov Identifier:
    NCT03150862
    Other Study ID Numbers:
    • BGB-290-104
    • 2017-001554-33
    First Posted:
    May 12, 2017
    Last Update Posted:
    May 31, 2022
    Last Verified:
    May 1, 2022