Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Neoplasms by Histologic Type

Gliosarcoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Tumor, Adult

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Pamiparib

Enzyme Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Alkylating Agents

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

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

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

Administered as specified in the treatment arm

Radiation

Study Director

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BeiGene USA, Inc.

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

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

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

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

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

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

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

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

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

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

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

Arm C: DE - Pamiparib + Temozolomide 20 mg

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

Arm C: DE - Pamiparib + Temozolomide 40 mg

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

Arm C: E- Pamiparib + Temozolomide 60 mg

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

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Unknown/Not Reported

Race/Ethnicity, Customized

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

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

Participants with At Least 1 TEAE

TEAE with Grade 3 or Higher

Treatment Emergent SAEs

TEAE Leading to Death

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

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

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

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

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

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

<1 cycle

1 cycle

2 cycles

3 cycles

4 cycles

5 cycles

6 cycles

7 cycles

>7 cycles

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

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

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

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

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

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

Arm C: DE- Pamiparib + Temozolomide 20 mg

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

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

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

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

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

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

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

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

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

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

Participants with at Lease 1 TEAE

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

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

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

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

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

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

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

Overall Study

Immunomodulating Agents

Arm A subjects with newly diagnosed disease will receive autologously derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Phase 1b subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide

Arm B subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide

Arm C subjects with newly diagnosed disease will receive allogeneic derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Arm A: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with TMZ maintenance

Autologous genetically modified gamma-delta T cells

Phase 1b and Arm B: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with D1 of TMZ 150mg/m2

Arms C: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with TMZ maintenance

Allogeneic genetically modified gamma-delta T cells

Trishna Goswami, MD

Stacey Bilinski

Louis Burt Nabors, MD

Sheila Medina-Torne

David Piccioni, M.D., PhD

Savanah Wiles

Timothy Cloughesy, M.D.

Jessica Malka

James Liu, MD

Akshitkumar Mistry, MD

Elicia Mangan

Mina Lobbous, MD, MSPH

Amy Heider

Pierre Giglio, MD

Louis B Nabors, MD

This multicenter, Phase 1b/2 study is being conducted to determine if the experimental cell therapy is safe, tolerable and can delay the return of cancer in patients with a newly diagnosed or recurrent glioblastoma multiforme (GBM) in combination with standard chemotherapy treatment temozolomide (TMZ). If there is a 25% or greater improvement in survival in this study then the therapy should be studied further.

This is a Phase 1b and 2 open-label cellular therapy trial using genetically modified gamma-delta (γδ) T cells or DeltEx Drug Resistant Immunotherapy (DRI). Gamma-delta T cells are a type of immune cell that may help the immune system recognize and kill cancer cells. The cells have been modified to make them resistant to the killing effects of chemotherapy such that they may be administered in combination with chemotherapy without being destroyed. The chemotherapy that is being used in this study is called temozolomide (TMZ) which is the standard-of-care used to treat glioblastoma patients. The DRI cells are given in combination with a standard dose of TMZ and are administered through a catheter directly into the brain where the tumor is located.

There are four arms to this study for eligible subjects with either newly diagnosed or relapsed IDH wild-type (IDH-wt) glioblastoma (GBM). Arm A will enroll newly diagnosed glioblastoma subjects to receive DRI cells derived from their own cells (autologous). The Phase 1b, Arms B and C will enroll subjects to receive DRI cells derived from a donor's cells (allogeneic). Subjects in the Phase 1b portion and Arm B must have relapsed disease, that is disease that has returned after initial treatment, while Arm A and C subjects must have newly diagnosed disease.

Prescreening subjects will have a standard-of-care surgical resection of their tumor. Once their preliminary eligibility is confirmed, they will have a Rickham catheter placed which is a device typically used to deliver chemotherapy into the brain that will be used to deliver the DRI cells directly to the tumor.

Following the surgical resection, subjects in Arm A will return to the study doctor's office/clinic to undergo a procedure called an apheresis. This procedure will isolate the immune cells from the blood to help make the DRI product for the subject. These cells include the gamma-delta T cells that will be used to make the DRI cells. Once the cells for the DRI product are made, they are frozen and stored for future use. In the Phase Ib and Arms B and C of the trial, a donor will undergo apheresis to provide the source of cells for the DRI product.

Following apheresis and confirmation that the required number of gamma-delta T cells were successfully collected; subjects in Arm A and C will begin the recommended or standard-of-care treatment for newly diagnosed GBM. This will include six weeks of chemotherapy with TMZ and radiation. Subjects will then have about a four week break prior to beginning the maintenance phase of treatment. Maintenance therapy includes five days of chemotherapy, every 28 days, which is repeated for six cycles. The previously frozen DRI product is thawed, prepared and is infused on the first day of each five-day cycle through the Rickham catheter. Subjects received a total of 6 infusions.

Subjects in the Phase Ib and Arm B will only receive one dose of TMZ along with the DRI product every 28 days for a total of six cycles.

Subjects will be observed for a of minimum 30 days after receiving the first dose of the DRI gamma-delta T cells. Subjects will be followed for potential side effects. The approximate duration of the study may be up to 15 years, or until disease progression or subjects withdraw from the study.

Arm A subjects with newly diagnosed disease will receive autologously derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Phase 1b and Arm B subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide

Arm C subjects with newly diagnosed disease will receive allogeneic derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma

A Phase 1b / 2 Open-label Study to Investigate the Safety, Tolerance and Efficacy of Drug Resistant Immunotherapy (DRI) With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide (TMZ) in Subjects With Recurrent or Newly Diagnosed Glioblastoma

Date of first dose to date of death by any cause

\<30% dose limiting toxicity (DLT) observed with dose

Assessment of safety is based on total number of treatment emergent adverse events and serious adverse events Assessment of safety is also based on change from baseline of clinical laboratory tests including change in liver function tests, renal function and complete blood counts Assessment of safety is also based on change from baseline of vital signs including heart rate, blood pressure, temperature and pulse oximetry

Assessment of tolerability is based on total number of treatment emergent adverse events and serious adverse events Assessment of tolerability is also based on change from baseline of clinical laboratory tests including change in liver function tests, renal function and complete blood counts Assessment of tolerability is also based on change from baseline of vital signs including heart rate, blood pressure, temperature and pulse oximetry

ORR is defined as the rate of the best overall response as complete response (CR) or partial response (PR).

Time to progression will be defined as the time from first dose until objective tumor progression

PFS will be defined as the time from first dose until objective tumor progression or death, whichever comes first.

Product characteristics that predict for maximal success of product creation:

Age of donor ( \<50 years of age, 51-65 years of age, \>65 years of age), Total white blood cell count and individual immune cell count (neutrophils, T cells, gamma delta T cells) of the apheresis product, Time to infusion of manufactured product of apheresis material (1 month, 2months)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma	NCT03150862	Brain and Centr...	Pamiparib TMZ Radiation	18 Years -	BeiGene
A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma	NCT05664243	Glioblastoma	Autologous gene... Allogeneic gene...	18 Years -	In8bio Inc.
A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma	NCT05664243	Glioblastoma	Autologous gene... Allogeneic gene...	18 Years -	In8bio Inc.

Spots Global Cancer Trial Database for neuroepithelial