A Multi-center Phase 2 Study of Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for the Treatment of Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- CatalYm GmbH
- 入组人数
- 31
- 试验地点
- 8
- 主要终点
- Pathological complete response rate
研究概览
简要总结
This is a multi-center, stratified and single-blinded Phase 2 trial of neoadjuvant immunotherapy in combination with the anti-GDF15 antibody visugromab (CTL-002) for the treatment of participants with MIBC set to undergo radical Cystectomy (RC)/Re-TURBT who cannot receive or refuse to receive cisplatin-based chemotherapy.
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
- Single (Participant)
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
- •Main Inclusion Criteria:
- •Signed and dated informed consent, and able to comply with the study procedures and any locally required authorization.
- •Male or female aged ≥ 18 years.
- •Histopathologically confirmed urothelial carcinoma.
- •Clinical Stage T2-T4aN0M0 MIBC.
- •Ineligible for cisplatin therapy per modified Galsky criteria or refuses cisplatin-based chemotherapy.
- •Eligible for radical cystectomy.
- •Pretreatment tumor material from transurethral resection of the bladder tumor (TURBT) must be available.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Adequate organ function (bone marrow, hepatic, renal function and coagulation).
排除标准
- •Pregnant or breastfeeding.
- •Received prior radiotherapy on the bladder tumor.
- •Received a partial cystectomy.
- •Any prior systemic anti-cancer therapy including investigational agents and immunotherapy.
- •Following cardio-vascular risk factors:
- •Myocardial infarction in the past 6 months before planned treatment start.
- •Uncontrolled heart failure.
- •Uncontrolled ventricular arrhythmia.
- •A peri/myocarditis in the past 3 months before planned treatment start. Note: Stable atrial fibrillation is permissive with or without anticoagulation if there was no decompensation in the past 3 months before planned treatment start.
- •Left ventricular ejection fraction (LVEF) < 50% measured by echocardiogram or MUGA.
- •QTcF ≥ 470 ms regardless of sex.
- •Any active autoimmune disease requiring systemic immunosuppressive treatments.
- •Any history of non-infectious pneumonitis < 6 months prior to Screening.
- •Any active inflammatory bowel disease such as Crohn's disease or ulcerative colitis which are generally excluded or active autoimmune thyroiditis present < 6 months prior to Screening.
- •History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (< 6 months prior to Screening).
研究组 & 干预措施
Combination with Placebo
Placebo + Checkpoint Inhibitor nivolumab
干预措施: Placebo (Drug)
Combination with Visugromab/Verum
visugromab (CTL-002) + Checkpoint Inhibitor nivolumab
干预措施: Visugromab (CTL-002) (Drug)
Combination with Placebo
Placebo + Checkpoint Inhibitor nivolumab
干预措施: Nivolumab (Drug)
Combination with Visugromab/Verum
visugromab (CTL-002) + Checkpoint Inhibitor nivolumab
干预措施: Nivolumab (Drug)
结局指标
主要结局
Pathological complete response rate
时间窗: min. 4 months
Rate of participants with complete pathological responses after IMP treatment as determined by local pathologist review
Radiological response rate according RECIST
时间窗: min. 4 months
Rate of participants with radiological responses according to RECIST 1.1 prior Radical Cystectomy/Re-TURBT as assessed by the Investigator/Radiologist
Pathological complete response rate
时间窗: min. 4 months
Rate of participants with complete pathological responses after IMP treatment as determined by local pathologist review
Radiological response rate according RECIST
时间窗: min. 4 months
Rate of participants with radiological responses according to RECIST 1.1 prior Radical Cystectomy/Re-TURBT as assessed by the Investigator/Radiologist
次要结局
- Adverse Events(min. 6 months)
- Treatment related delay of surgery(min. 6 months)
- Cmax following the first dose of Visugromab (CTL-002)(1 day)
- AUC following the first dose of Visugromab (CTL-002)(28 days)
- Half-life of Visugromab (CTL-002)(min. 3 months)
- GDF-15 serum levels(1 day)
- Pathological complete response rate(min. 4 months)
- Radiological response rate according RECIST(Min. 4 months)
- Major pathological response rate(Min. 4 months)
- Evaluation of EFS (Event-free Survival)(12 months after Radical Cystectomy/Re-TURBT)
- OS (Overall Survival)(15 months)
- Evaluation of TTR (Time to Relapse)(12 months after Radical Cystectomy/Re-TURBT)
- Visugromab-induced anti-drug antibodies (ADA) development.(min. 5 months)
- Adverse Events(min. 6 months)
- Treatment related delay of surgery(min. 6 months)
- Cmax following the first dose of Visugromab (CTL-002)(1 day)
- AUC following the first dose of Visugromab (CTL-002)(28 days)
- Half-life of Visugromab (CTL-002)(min. 3 months)
- GDF-15 serum levels(1 day)
- Pathological complete response rate(min. 4 months)
- Radiological response rate according RECIST(Min. 4 months)
- Evaluation of EFS (Event-free Survival)(12 months after Radical Cystectomy/Re-TURBT)
- OS (Overall Survival)(15 months)
- Evaluation of TTR (Time to Relapse)(12 months after Radical Cystectomy/Re-TURBT)
- Visugromab-induced anti-drug antibodies (ADA) development.(min. 5 months)