Phase 2
Completed N=116
A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma
Source: ClinicalTrials.gov NCT03150862 ↗Enrolled (actual)
116
Serious AEs
36.2%
Results posted
May 2022
Primary outcomePrimary: Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE — 0; 0; 2; 1 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE |
0; 0; 2; 1; 0; 3 | — |
| PRIMARY Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE |
3; 8; 9; 9; 9; 8 | — |
| PRIMARY Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements |
0; 0 | — |
| PRIMARY Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria |
65.6 | — |
| PRIMARY Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria |
10.7 | — |
| PRIMARY Phase 1b Arm C: Number of Cycles of Treatment Received by Participants |
2; 3; 4; 0; 1; 2 | — |
| PRIMARY Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant |
97.5; 107.6; 13.6; 28.2 | — |
| SECONDARY Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib |
891.3; 1817.0; 1848.3; 2239.9; 2134.3; 1893.3 | — |
| SECONDARY Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria |
66.7; 100.0; 42.9; 80.0 | — |
| SECONDARY Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria |
55.6; 71.4 | — |
| SECONDARY Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria |
0; 16.7; 0; 3.1; 0 | — |
| SECONDARY Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria |
0; 33.3; 0; 37.6; 40.0; 0 | — |
| SECONDARY Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria |
6.44; 10.32; 11.7; NA | — |
| SECONDARY Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria |
3.12; 8.94; 2.56; 4.44; 5.75; 1.81 | — |
| SECONDARY Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS) |
14.46; 13.44; 10.25; 12.71; 14.23; 6.00 | — |
| SECONDARY Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
40; 29; 25; 19; 18; 11 | — |
| SECONDARY Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements |
0; 0 | — |
| SECONDARY Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants |
3; 8; 9; 8; 2; 7 | — |
| SECONDARY Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant |
109.0; 109.5; NA; 19.6 | — |
Eligibility Criteria
Key Inclusion Criteria: All participants
- Age ≥ 18 years old.
- Confirmed diagnosis of glioblastoma (WHO Grade IV).
- Agreement to provide archival tumor tissue for exploratory biomarker analysis
- Ability to undergo serial MRIs.
- Eastern Cooperative Oncology Group (ECOG) status ≤ 1.
- Adequate hematologic and end-organ function
- Females of childbearing potential and non-sterile males must agree to use highly effective methods of birth control throughout the course of study and at least up to 6 months after last dosing.
- Ability to swallow whole capsules.
Participants in Arms A and B (not Arm C) must meet inclusion criteria # 9 - 11:
- No previous treatment for GBM except surgery.
- Able to start radiation therapy ≤ 49 days after surgery but ≥ 14 days after a biopsy or ≥28 days after an open biopsy or craniotomy with adequate wound healing.
- Documented unmethylated MGMT promoter status.
Participants in Arm C Escalation (Phase 1b) must meet inclusion criteria # 12 - 15:
- Documentation of MGMT promoter status
- No prior systemic chemotherapy other than TMZ for GBM.
- Histologically confirmed secondary glioblastoma
- Disease that is evaluable or measurable as defined by Response Assessment in Neuro-Oncology (RANO) criteria
Participants in Arm C Expansion (Phase 2), must meet criteria # 16 - 18:
- Histologically confirmed de novo (primary) glioblastoma with unequivocal first progressive disease (PD) after RT with concurrent/adjuvant TMZ chemotherapy
- Disease that is measurable as defined by RANO criteria
- Documentation of MGMT promoter status
Key Exclusion Criteria: All participants
- Prior chemotherapy, biologic therapy, immunotherapy or investigational agents ≤21 days prior to start of study treatment.
- Toxicity of ≥ Grade 2 from prior therapy.
- Major surgery or significant other injury ≤ 4 weeks prior to start of study treatment.
- History of other active malignancies within 2 years with exception of (i) adequately treated in situ cancer of the cervix, (ii) non-melanoma skin cancer, or (iii) localized adequately treated cancer with curative intent or malignancy diagnosed > 2 years ago with no evidence of disease and no treatment ≤ 2 years prior to study treatment.
- Active infection requiring systemic treatment.
- Known human immunodeficiency virus (HIV) or active viral hepatitis.
- Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease, ventricular arrhythmia or Cerebrovascular Accident (CVA) ≤ 6 months prior to start of treatment.
- Active clinically significant gastrointestinal disease.
- Active bleeding disorder ≤ 6 months prior to start of treatment.
- Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants.
- Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.
- Pregnant or nursing females.
- Significant intercurrent illness that may result in participant's death prior to death from glioblastoma.
Arms B and C Only:
- Known hypersensitivity to any component of TMZ or decarbazine (DTIC).
- Have hereditary problems of galactose intolerance
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT03150862). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.