An Open-Label, Multi-Center Trial of INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With REGN2810 in Subjects With Newly-Diagnosed Glioblastoma (GBM)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 52
- 试验地点
- 41
- 主要终点
- Percentage of Participants with Adverse Events (AEs)
研究概览
简要总结
Phase 1/2 trial to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with cemiplimab (REGN2810), with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM).
详细描述
This is a phase 1/2, open-label, multi-center trial to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with cemiplimab in subjects with newly-diagnosed glioblastoma (GBM). INO-5401 and INO-9012 will be delivered by intramuscular (IM) injection followed by electroporation (EP) in combination with cemiplimab and chemoradiation and radiation. There will be 2 cohorts in this trial. Cohort A will be participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B will be participants with a tumor with a MGMT methylated promoter or who have indeterminate MGMT status. Both cohorts will receive INO-5401 and INO-9012 and cemiplimab at the same doses and on the same dosing schedule, and both cohorts will receive radiation and temozolomide (TMZ), if clinically indicated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •* Newly-diagnosed brain cancer with histopathological diagnosis of GBM;
- •* Karnofsky Performance Status (KPS) rating of \>/=70 at baseline;
- •* Receive dexamethasone equivalent dose \/= three days prior to Day 0;
- •* Recovery from the effects of prior GBM surgery as defined by the Investigator;
- •* Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator;
- •* Adequate organ function as demonstrated by hematological, renal, hepatic laboratory assessments;
- •* Agree that during the trial, men will not father a child, and women cannot be or become pregnant. Participants must be of non-child bearing potential or agree to use one highly effective or combined contraceptive methods that result in a failure rate of \<1% per year during the treatment period and at least through week 12 after last dose;
- •* Ability to tolerate magnetic resonance imaging (MRI).
排除标准
- •Presence of greater than 1 cm x 1 cm residual tumor enhancement on postoperative MRI;
- •Multifocal disease or leptomeningeal disease (LM) disease on post-operative MRI;
- •Not scheduled to start radiation within 42 days of surgical resection of tumor;
- •Dexamethasone equivalent dose >2 mg per day;
- •Prior treatment with an agent that blocks the PD-1/PD-Ligand 1 pathway;
- •Receipt of previous approved or investigative immune modulatory agent within 28 days of receiving the first dose of treatment;
- •Prior treatment with idelalisib;
- •Past, current or planned treatment with tumor treatment fields; oncolytic viral treatment; or prior exposure to an investigational agent or device within 28 days of receiving the first dose of treatment;
- •Allergy or hypersensitivity to cemiplimab or to any of its excipients;
- •History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments;
- •Ongoing or recent (within 5 years) evidence of autoimmune disease that required treatment with systemic immunosuppressive treatments;
- •Diagnosis of immunodeficiency or treatment with systemic immunosuppressive therapy within 28 days prior to the first dose of trial treatment, other than dexamethasone for the underlying disease under investigation, as noted in the inclusion criteria;
- •History of clinically significant, medically unstable disease which, in the judgment of the investigator, would jeopardize the safety of the subject, interfere with trial assessments or endpoint evaluation, or otherwise impact the validity of the trial results.
研究组 & 干预措施
Cohort A: Unmethylated MGMT Promoter
Cohort A will include participants with a glioblastoma tumor with an unmethylated MGMT promoter. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ; only during radiation therapy), if clinically indicated.
干预措施: Temozolomide (Drug)
Cohort A: Unmethylated MGMT Promoter
Cohort A will include participants with a glioblastoma tumor with an unmethylated MGMT promoter. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ; only during radiation therapy), if clinically indicated.
干预措施: INO-5401 (Biological)
Cohort A: Unmethylated MGMT Promoter
Cohort A will include participants with a glioblastoma tumor with an unmethylated MGMT promoter. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ; only during radiation therapy), if clinically indicated.
干预措施: INO-9012 (Biological)
Cohort A: Unmethylated MGMT Promoter
Cohort A will include participants with a glioblastoma tumor with an unmethylated MGMT promoter. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ; only during radiation therapy), if clinically indicated.
干预措施: Cemiplimab (Biological)
Cohort A: Unmethylated MGMT Promoter
Cohort A will include participants with a glioblastoma tumor with an unmethylated MGMT promoter. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ; only during radiation therapy), if clinically indicated.
干预措施: Radiation Therapy (Radiation)
Cohort B: Methylated MGMT Promoter
Cohort B will include participants with a glioblastoma tumor with a methylated MGMT promoter or with indeterminate MGMT status. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ), if clinically indicated. Participants will continue to receive TMZ following radiation therapy, for up to six additional cycles, if clinically indicated.
干预措施: INO-5401 (Biological)
Cohort B: Methylated MGMT Promoter
Cohort B will include participants with a glioblastoma tumor with a methylated MGMT promoter or with indeterminate MGMT status. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ), if clinically indicated. Participants will continue to receive TMZ following radiation therapy, for up to six additional cycles, if clinically indicated.
干预措施: INO-9012 (Biological)
Cohort B: Methylated MGMT Promoter
Cohort B will include participants with a glioblastoma tumor with a methylated MGMT promoter or with indeterminate MGMT status. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ), if clinically indicated. Participants will continue to receive TMZ following radiation therapy, for up to six additional cycles, if clinically indicated.
干预措施: Cemiplimab (Biological)
Cohort B: Methylated MGMT Promoter
Cohort B will include participants with a glioblastoma tumor with a methylated MGMT promoter or with indeterminate MGMT status. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ), if clinically indicated. Participants will continue to receive TMZ following radiation therapy, for up to six additional cycles, if clinically indicated.
干预措施: Radiation Therapy (Radiation)
Cohort B: Methylated MGMT Promoter
Cohort B will include participants with a glioblastoma tumor with a methylated MGMT promoter or with indeterminate MGMT status. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ), if clinically indicated. Participants will continue to receive TMZ following radiation therapy, for up to six additional cycles, if clinically indicated.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events (AEs)
时间窗: From Day 0 to 30 days after the last dose of study treatment (non-serious AEs) and to 6 months after the last dose of study treatment (immune-related AEs, AEs of special interest and serious AEs) up to approximately 24 months
次要结局
- Overall survival at 18 months (OS18)(At Month 18)
- Change from Baseline in Interferon-gamma Secreting T Lymphocytes in Peripheral Blood Mononuclear Cells (PBMCs)(From Day 0 to last dose of study treatment up to approximately 18 months)
- Change from Baseline in T-Cell Phenotypes in PBMCs(From Day 0 to last dose of study treatment up to approximately 18 months)
- Change from Baseline in T Cell Receptor (TCR) Subtypes in PBMCs(From Day 0 to last dose of study treatment up to approximately 18 months)
- Change from Baseline in Antigen-Specific Humoral Response(From Day 0 to last dose of study treatment up to approximately 18 months)