A Phase 1 Open-Label Study of Genetically Engineered Oncolytic HSV-1 (C5252) Expressing IL-12 and Anti-PD-1 Antibody in Patients With Recurrent or Progressive Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 51
- 试验地点
- 2
- 主要终点
- Characterize Dose Limiting Toxicities
研究概览
简要总结
This is a Phase 1 open label, first in human study of C5252 monotherapy designed to determine the safety and tolerability of a single intratumoral (IT) injection of C5252 in patients with recurrent or progressive glioblastoma (GBM).
详细描述
This is a Phase 1 open label, first in human study of C5252 monotherapy designed to determine the safety and tolerability of a single IT injection of C5252 in patients with recurrent or progressive GBM. The Part 1 portion of the study is a 3+3 design to evaluate escalating doses of C5252. Total enrollment will depend on the toxicities and/or activity observed, with approximately 36 evaluable participants enrolled. Once the recommended dose (RD) is identified from Part 1, Part 2 Dose Expansion will enroll up to 15 additional participants to further assess the safety, tolerability, and preliminary efficacy of a single IT injection of C5252 monotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Signed and dated approved informed consent form (ICF) before any protocol-directed screening procedures are performed.
- •Participants must have histopathologically confirmed recurrent supratentorial glioblastoma.
- •Participants must have progressed after at least 1 line but no more than 2 lines of therapy.
- •Evidence of progression by RANO criteria based on MRI scan.
- •Residual lesion must be ≥ 1.0 cm and < 5.5 cm contrast-enhancing in diameter as determined by MRI.
- •Age ≥ 18 years.
- •Karnofsky Performance Score (KPS) ≥
- •Life expectancy > 12 weeks.
- •Participants must have normal organ and marrow function.
- •Participants must commit to the use of a reliable method of birth control.
- •Resolution of all AEs due to previous therapies to ≤ Grade 1 or baseline.
- •Capable of understanding and complying with protocol requirements.
排除标准
- •Inability to undergo MRI examination for any reason.
- •A contrast-enhancing brain tumor that does not meet protocol criteria.
- •Prior history of encephalitis, multiple sclerosis, or other CNS infection.
- •Clinical diagnosis of Li-Fraumeni Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways.
- •Required steroid increase within 2 weeks prior to date of C5252 administration.
- •Systemic therapy with immunosuppressive agents within 28 days prior to date of C5252 administration.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other medical condition that precludes surgery. Also, psychiatric illness/social situations that would limit compliance with study requirements.
- •Bleeding diathesis, or requirement for anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery or biopsy.
- •Current diagnosis of other cancer except in situ cervical cancer, basal or squamous cell carcinoma of the skin.
- •Requires continued concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir).
- •Pregnant or lactating.
- •Prior organ transplantation.
- •Active hepatitis B virus, hepatitis C virus, or a positive serological test at Screening.
- •Active oral herpes lesion at Screening.
- •Congestive heart failure (> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest), or clinically significant cardiac arrhythmias.
- •History of allergic reactions attributed to compounds of similar biological composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody.
- •Active infection with SARS-CoV-2 virus.
- •Other systemic conditions or organ abnormalities that, in the opinion of the Investigator, may interfere with the conduct and/or interpretation of the current study.
结局指标
主要结局
Characterize Dose Limiting Toxicities
时间窗: Up to 28 days from C5252 injection
Incidence of DLTs
Identify the maximum tolerated dose (MTD) and/or the RD of C5252
时间窗: Up to 28 days from C5252 injection
Incidence of DLTs
Evaluate the safety and tolerability of C5252
时间窗: Up to 28 days from C5252 injection
Number of participants in dose escalating cohorts with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
次要结局
- Overall response rate (ORR)(Up to 2 years from C5252 injection)
- Evaluate the PK of C5252(Up to 2 years from C5252 injection)
- Evaluate the viral shedding of C5252(Up to 2 years from C5252 injection)
- Overall Survival (OS)(Up to 2 years from C5252 injection)
- Progression-free survival (PFS)(Up to 2 years from C5252 injection)