A Randomized, Open-Label, Phase 2 Study of a Patient-Specific Vaccine Targeting Neoantigens in Combination With Immune Checkpoint Blockade for Patients With Colon Cancer With Minimal Residual Disease Following Surgical Resection and Standard Adjuvant Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 1
- 试验地点
- 3
- 主要终点
- Incidence and Severity of Adverse Events
研究概览
简要总结
The primary objective is to assess and characterize the antitumor activity and safety and tolerability of adjuvant treatment with an individualized neoantigen vaccine called GRT-C901/GRT-R902 (chimpanzee adenovirus [ChAd] and self-amplifying messenger RNA [samRNA] vectors), in combination with checkpoint inhibitors. Antitumor activity will be based on molecular response in patients with colon cancer who have circulating tumor deoxyribonucleic acid (ctDNA) following surgical resection.
详细描述
Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations present peptides containing these mutations as non-self antigens in the context of human leukocyte antigens (HLAs) on the tumor cell surface. A fraction of mutated peptides results 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, ChAd as prime and GRT-R902, samRNA as boost) to stimulate an immune response. This study (GRANITE-ADJUVANT) will explore the anti-tumor activity of this individualized, patient specific immunotherapy in combination with checkpoint inhibitors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
GRT-C901/GRT-R902 Vaccine arm
After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
干预措施: GRT-C901 (Drug)
GRT-C901/GRT-R902 Vaccine arm
After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
干预措施: GRT-R902 (Drug)
GRT-C901/GRT-R902 Vaccine arm
After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
干预措施: Atezolizumab (Drug)
GRT-C901/GRT-R902 Vaccine arm
After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
干预措施: Ipilimumab (Drug)
GRT-C901/GRT-R902 Vaccine arm
After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
干预措施: Adjuvant chemotherapy (Drug)
Observation arm
After surgical resection, patients who are ctDNA positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction and randomization. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will be observed via study visits occur every 12 weeks.
干预措施: Adjuvant chemotherapy (Drug)
结局指标
主要结局
Incidence and Severity of Adverse Events
时间窗: Up to ~100 days after last study treatment (Up to 62 weeks)
The incidence and severity will be assessed for treatment-emergent adverse events (TEAEs), immune-related AEs (irAEs), treatment-related AEs, serious AEs (SAEs), AEs leading to death while patients are on treatment or up to 100 days after the last study treatment, AEs leading to dose delays or dose discontinuation, and AEs leading to discontinuation of study treatment using National Cancer Institute (NCI) Criteria for Adverse Events (CTCAE) v5.0
Percentage of Patients with a ≥50% Decrease from Baseline in Circulating Tumor deoxyribonucleic acid (ctDNA)
时间窗: Baseline and up to ~24 months
次要结局
- Recurrence-free survival (RFS) per Investigator(From time of randomization until first recurrence of the same cancer, or death (Up to ~36 months))
- Longest Duration of Molecular response of ctDNA Decrease from Baseline(Baseline and up to ~24 months)
- Success of Vaccine Manufacture(Up to 28 days before Day 1 of study drug administration)
- Overall Survival (OS)(From time of randomization until death due to any cause (Up to ~36 months))
- T-cell response using Peripheral Blood Mononuclear Cells (PBMCs)(Up to ~24 months)
- Disease-free survival (DFS) per Investigator(From time of randomization until first recurrence of any cancer, or death (Up to ~36 months))
- Conversion of Patients with ctDNA at Baseline to Undetectable ctDNA as Assessed via a Polymerase Chain Reaction (PCR)-Based Assay(Baseline and up to ~24 months)