An International Phase 1/2 Study of GRT-C901/GRT-R902, a Neoantigen Cancer Vaccine, in Combination With Immune Checkpoint Blockade for Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 19
- 主要终点
- Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902
研究概览
简要总结
The purpose of this study is to evaluate the safety, dose, immunogenicity and early clinical activity of GRT-C901 and GRT-R902, a personalized neoantigen cancer vaccine, in combination with nivolumab and ipilimumab, in patients with metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal adenocarcinoma, and metastatic urothelial cancer.
详细描述
Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations can present peptides containing these mutations as non-self antigens in the context of HLA on the tumor cell surface. A fraction of mutated peptides result in neoantigens capable of generating T-cell responses that exclusively target tumor cells. Sensitive detection of these mutations allows for the identification of neoantigens unique to each patient's tumor to be included in a personalized cancer vaccine that targets these neoantigens. This vaccine regimen uses two vaccine vectors as a heterologous prime/boost approach (GRT-C901 first followed by GRT-R902) to stimulate an immune response. This study will explore the safety and early clinical activity of this patient-specific immunotherapy intended to induce T-cell responses specific for neoantigens.
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
- •Provide a signed and dated informed consent form prior to initiation of study-specific procedures.
- •Patients with the indicated advanced or metastatic solid tumor as follows:
- •NSCLC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy (note: patients who have received anti-PD-(L)1 monotherapy are eligible)
- •GEA who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy
- •mUC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy
- •CRC-MSS who are receiving first line systemic therapy or who are planned for or have received no more than 1 cycle of second line systemic therapy including a fluoropyrimidine and oxaliplatin or irinotecan
- •18 years of age or older
- •ECOG Performance Status 0 or 1
- •Lesion amenable to biopsy
- •Measurable disease according to RECIST v1.1
- •Have adequate organ function, as measured by laboratory values (criteria listed in protocol)
排除标准
- •Tumors with genetic characteristics as follows:
- •For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK
- •For CRC and GEA, patients with known MSI-high disease based on institutional standard
- •For CRC, patients with a known BRAF V600E mutation or patients with peritoneal carcinomatosis and for GEA, patients with peritoneal carcinomatosis as their only evidence of disease
- •Patients with known central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Known exposure to chimpanzee adenovirus or any history of anaphylaxis in reaction to a vaccination or allergy or hypersensitivity to study drug components
- •Bleeding disorder (eg., factor deficiency, coagulopathy) or history of significant bruising or bleeding following IM injections or blood draws
- •Complete inclusion and exclusion criteria are listed in the clinical study protocol.
结局指标
主要结局
Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902
时间窗: Up to approximately 6 months
Objective Response Rate (ORR) in Phase 2 using RECIST v1.1
时间窗: Initiation of study treatment until disease progression (up to approximately 27 months)
Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
时间窗: Initiation of study treatment through 100 days post-last dose (up to approximately 27 months)
次要结局
- Objective Response Rate (ORR) in Phase 1 using RECIST v1.1(Initiation of study treatment until disease progression (up to approximately 4 years))
- Progression-free survival (PFS)(Up to approximately 4 years)
- Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902(Baseline to end of treatment (up to approximately 12 months))
- Clinical benefit rate (using RECIST v1.1)(Initiation of study treatment until disease progression (up to approximately 4 years))
- Overall survival (OS)(Up to approximately 4 years)
- Duration of response (DOR) using RECIST v1.1(Initiation of study treatment until disease progression (up to approximately 4 years))
- Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing(Study enrollment to initiation of study treatment (up to approximately 6 months))