NCT06534983进行中（未招募）2 期
A Randomized Phase II, Double-blind, Multicenter Study Evaluating the Efficacy and Safety of Autogene Cevumeran Plus Nivolumab Versus Nivolumab as Adjuvant Therapy in Patients With High-risk Muscle-invasive Urothelial Carcinoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 62
- 试验地点
- 199
- 主要终点
- Investigator-assessed (INV) Disease-free Survival (DFS)
研究概览
简要总结
The original purpose of this study was to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants with high risk MIUC. In this study participants will be enrolled in a safety run-in phase to receive autogene cevumeran + nivolumab. This phase will be conducted to monitor and ensure the safety of study participants. After all participants in the safety run-in have been enrolled to receive autogene cevumeran + nivolumab, further participants will be randomized in either autogene cevumeran + nivolumab or the nivolumab monotherapy arm.
Following the Sponsor's decision to phase out the study, as of Protocol Version 5, the primary purpose of the study is to ensure treatment continuity and safety for the participants who continue to participate in the study and receive study treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Participants must have the capacity to participate/enroll in the study and to provide informed consent
- •Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma [TCC]) of the bladder or upper urinary tract
- •Tumor-node-metastasis (TNM ) classification (Union for International Cancer Control [UICC]/American Joint Committee on Cancer [AJCC] 7th edition) at pathological examination of surgical resection specimen of (y)pT3-4 or (y)pN+ and M0
- •Surgical resection of MIUC of the bladder or upper tract
- •Participants who have received neoadjuvant chemotherapy (NAC), including antibody drug-conjugate, either alone or in combination with a checkpoint inhibitor (CPI), are eligible
- •Participants who have not received any prior NAC are also eligible, provided they meet one of the following criteria, which would make them ineligible to receive adjuvant cisplatin-based therapy: participant refusal, cisplatin ineligibility or investigator decision
- •Tumor tissue must be provided for biomarker analysis
- •Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 28 days prior to randomization
- •Full recovery from cystectomy or nephroureterectomy within 120 days following surgery
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- •Negative human immunodeficiency virus (HIV) test at screening
- •Negative hepatitis B surface antigen (HbsAg) test at screening
- •Positive hepatitis B surface antibody (HBsAb), or a negative HBsAb at screening accompanied by either of the following: negative total hepatitis B core antibody (HBcAb) or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) < 500 international units/milliliter (IU/mL)
- •Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
排除标准
- •Partial cystectomy in the setting of bladder cancer primary tumor or partial nephroureterectomy in the setting of renal pelvis primary tumor
- •Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
- •Adjuvant chemotherapy, immunotherapy, or radiation therapy for UC following surgical resection
- •Prior active malignancies within 3 years prior to randomization
- •Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
研究组 & 干预措施
Nivolumab
Active Comparator
Participants will receive 480 milligrams (mg) of nivolumab, IV, once every 4 weeks (Q4W) for 1 year.
干预措施: Nivolumab (Drug)
Autogene Cevumeran + Nivolumab
Experimental
Participants will receive autogene cevumeran along with nivolumab intravenously (IV) at a recommended dose at specified timepoints.
干预措施: Autogene Cevumeran (Drug)
Autogene Cevumeran + Nivolumab
Experimental
Participants will receive autogene cevumeran along with nivolumab intravenously (IV) at a recommended dose at specified timepoints.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Investigator-assessed (INV) Disease-free Survival (DFS)
时间窗: Randomization until the first recurrence of disease or death from any cause, whichever occurs first (approximately 6 years)
Disease recurrence is defined as any of the following: * Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes); * Urinary tract recurrence of UC (excluding low-grade non-muscle-invasive bladder cancer \[NMIBC\]); * Distant metastasis of UC.
次要结局
- Overall Survival (OS)(Randomization until the date of death from any cause (approximately 6 years))
- INV-DFS in Programmed Death Ligand-1 (PD-L1) Expression ≥ 1% Population(Randomization until first occurrence of a documented disease recurrence or death from any cause, whichever occurs first (approximately 6 years))
- INV-Distant Metastasis-free Survival (DMFS)(Randomization to the date of diagnosis of distant (i.e., non-locoregional) metastases (approximately 6 years))
- Number of Participants With Adverse Events (AEs)(Up to approximately 22 months)
- Change From Baseline in Participant-reported Pain, Physical Function, Role Function and Quality of Life (QoL) as Assessed Using European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-C30 (EORTC QLQ-C30)(From Day 1 up to approximately 25 months)
- Number of Participants With Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-reported Outcomes - Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)(From Day 1 up to Cycle 21 (cycle length=28 days))
- Number of Participants Experiencing AE Burden due to Treatment as Assessed by EORTC Item Library 46 (IL46)(From Day 8 up to Cycle 21 (cycle length=28 days))
- Change from Baseline in Symptomatic Treatment Toxicities as Assessed by NCI PRO-CTCAE(From Day 1 up to Cycle 21 (cycle length=28 days))
研究者
研究点 (199)
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