A Phase 3 Study Evaluating Sacituzumab Tirumotecan Plus Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) as Induction Therapy, Followed by Local Therapy With Chemoradiation and MK-3475A Consolidation Versus Local Therapy With Chemoradiation in Participants With MIBC Who Elect Bladder Preservation
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 400
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of bladder cancer that has spread into the muscle layer of the bladder but has not spread to other distant parts of the body.
The usual treatment for MIBC is surgery to remove the bladder but some people choose to have other treatments, such as chemoradiotherapy (CRT), instead of surgery so they can keep their bladder.
Researchers want to know if giving 2 trial treatments with CRT can treat MIBC. One trial treatment is called sacituzumab tirumotecan (sac-TMT) and the other trial treatment is called subcutaneous (SC) pembrolizumab (or pembrolizumab and berahyaluronidase alfa). The main goal of this trial is to learn if participants who receive sac-TMT, SC pembrolizumab, and CRT live longer without their cancer growing, spreading, or coming back compared to those who receive CRT alone.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Has a diagnosis of muscle-invasive bladder cancer (MIBC) (cT2-T4aN0-N1)
- •Has clinically nonmetastatic bladder cancer (N0-N1M0)
- •Is either ineligible for radical cystectomy or has opted for bladder preservation and is planned to receive chemoradiotherapy (CRT)
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has known presence of diffuse carcinoma in situ (CIS) throughout the bladder
- •Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- •Has received prior pelvic/local radiation therapy for any reason or any systemic antineoplastic treatment for MIBC
- •Has not recovered to Grade ≤1 or baseline from AE associated with anticancer therapy before randomization
- •Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments
研究组 & 干预措施
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Rescue Medications (Drug)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Pembrolizumab and Berahyaluronidase alfa (Biological)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Conventional Radiotherapy (Radiation)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Hypofractionated radiotherapy (Radiation)
Chemoradiotherapy
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
干预措施: MMC (Drug)
Chemoradiotherapy
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
干预措施: Conventional Radiotherapy (Radiation)
Chemoradiotherapy
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
干预措施: Hypofractionated radiotherapy (Radiation)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: 5-FU (Drug)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Sac-TMT (Biological)
Chemoradiotherapy
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
干预措施: Cisplatin (Drug)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Capecitabine (Drug)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: MMC (Drug)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Gemcitabine (Drug)
Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy
Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses.
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).
干预措施: Cisplatin (Drug)
Chemoradiotherapy
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
干预措施: 5-FU (Drug)
Chemoradiotherapy
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
干预措施: Capecitabine (Drug)
Chemoradiotherapy
CRT (radiotherapy [RT] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: Up to approximately 60 months
EFS is defined as the time from randomization to the first occurrence of any of the following events, as assessed by blinded independent central review (BICR): residual/recurrent MIBC, or locoregional disease, or distant metastases as assessed by imaging and/or biopsy results, or death from any cause. The EFS for all participants will be presented.
次要结局
- Overall Survival (OS)(Up to approximately 90 months)
- Distant Metastasis-Free Survival (DMFS)(Up to approximately 90 months)
- Bladder Intact (BI)-EFS(Up to approximately 90 months)
- Time to Occurrence of Non-Muscle-Invasive Bladder Cancer (NMIBC)(Up to approximately 90 months)
- Disease-Specific Survival(Up to approximately 90 months)
- Rate of Radical Cystectomy(Up to approximately 90 months)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 90 months)
- Number of Participants Who Discontinue Study Intervention Due to an AE(Up to approximately 90 months)