A Phase 1/2 Study of V940 Plus Pembrolizumab With or Without Enfortumab Vedotin in Muscle-Invasive Urothelial Carcinoma (MIUC) (INTerpath-005)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 230
- 试验地点
- 144
- 主要终点
- Adjuvant Cohort: Disease Free Survival (DFS)
研究概览
简要总结
Researchers are looking for new ways to treat people with high-risk muscle-invasive urothelial carcinoma (MIUC). Urothelial carcinoma is a type of bladder cancer that begins in cells that line the inside of the bladder and other parts of the urinary tract, such as part of the kidneys, ureters, and urethra. People with MIUC usually have chemotherapy before surgery, then surgery to remove the cancer. Chemotherapy is a type of medicine to destroy cancer cells or stop them from growing. After surgery, some people receive more treatment to prevent cancer from returning. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Enfortumab vedotin (EV) is an antibody drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to learn if giving intismeran autogene (the study treatment) with pembrolizumab can prevent MIUC from returning after surgery. Intismeran autogene (also called mRNA-4157) is designed to treat each person's cancer by helping the person's immune system identify and kill cancer cells based on certain proteins found on those cancer cells.
The goals of this study are to learn if people who receive intismeran autogene and pembrolizumab are alive and cancer free longer than those who receive placebo and pembrolizumab, and to learn about the safety of intismeran autogene, pembrolizumab, and EV, and if people tolerate them.
详细描述
Enrollment of participants into the Phase 1 Perioperative Cohort of this study is planned to start in approximately April of 2025.
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
- Double (Participant, Investigator)
盲法说明
The Phase 2 Adjuvant Cohort of study will be conducted as a double-blind study under in-house blinding procedures. Intismeran autogene and placebo will be prepared and dispensed by unblinded pharmacists and administered in a blinded fashion by blinded personnel. The participants and the investigators who are involved in the study intervention administration will be unaware of the intervention assignments.
The Phase 1 Perioperative Cohort will be conducted as an open-label study. Participants and investigators will be aware of the intervention assignments.
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 histological diagnosis of urothelial carcinoma (UC)
- •Must provide blood samples per protocol, to enable intismeran autogene production, and circulating tumor deoxyribonucleic acid testing
- •Has an Eastern Cooperative Oncology Group performance status of 0 to 2 assessed within 7 days before randomization
- •Must provide a formalin-fixed paraffin-embedded tumor tissue sample for next generation sequencing
- •Adjuvant Cohort:
- •Has high-risk pathologic disease after radical resection
- •For participants who have not received cisplatin-based neoadjuvant chemotherapy, are ineligible to receive cisplatin according to protocol pre-defined criteria
- •Perioperative Cohort:
- •Is deemed eligible for RC and PLND and agrees to undergo curative intent standard RC and PLND and neoadjuvant and adjuvant treatment per protocol
- •Is ineligible to receive cisplatin according to protocol pre-defined criteria
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Has known additional malignancy that is progressing or has required active treatment ≤3 years prior to study randomization
- •Has current pneumonitis/interstitial lung disease
- •Has active infection requiring systemic therapy
- •Has active hepatitis B and hepatitis C virus infection
- •Adjuvant Cohort:
- •Has received prior systemic anticancer therapy
- •Has received prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy for MIUC
- •Has severe hypersensitivity to either intismeran autogene or pembrolizumab (MK-3475) and/or any of their excipients
- •Perioperative Cohort:
- •Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
- •Has severe hypersensitivity to either intismeran autogene, pembrolizumab, or EV and/or any of their excipients
- •Has ongoing sensory or motor neuropathy
- •Has active keratitis or corneal ulcerations
研究组 & 干预措施
Adjuvant Cohort: Pembrolizumab + Intismeran autogene
Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of intismeran autogene. Intismeran autogene doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
干预措施: Pembrolizumab (Biological)
Adjuvant Cohort: Pembrolizumab + Intismeran autogene
Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of intismeran autogene. Intismeran autogene doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
干预措施: Intismeran autogene (Biological)
Adjuvant Cohort: Pembrolizumab + Placebo
Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of placebo. Placebo doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
干预措施: Pembrolizumab (Biological)
Adjuvant Cohort: Pembrolizumab + Placebo
Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of placebo. Placebo doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
干预措施: Placebo (Other)
Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery
Participants will receive neoadjuvant treatment with up to 4 cycles of pembrolizumab plus EV and 1 to 4 doses of intismeran autogene, followed by radical cystectomy [RC] plus pelvic lymph node dissection [PLND], and then adjuvant treatment with up to 13 cycles of pembrolizumab plus up to 5 cycles of EV and 5 to 8 doses of intismeran autogene (for a total of 9 neoadjuvant plus adjuvant Intismeran autogene doses), or until any of the protocol-specified criteria for discontinuation of study intervention are met. The total duration of treatment is up to approximately 16 months.
干预措施: Pembrolizumab (Biological)
Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery
Participants will receive neoadjuvant treatment with up to 4 cycles of pembrolizumab plus EV and 1 to 4 doses of intismeran autogene, followed by radical cystectomy [RC] plus pelvic lymph node dissection [PLND], and then adjuvant treatment with up to 13 cycles of pembrolizumab plus up to 5 cycles of EV and 5 to 8 doses of intismeran autogene (for a total of 9 neoadjuvant plus adjuvant Intismeran autogene doses), or until any of the protocol-specified criteria for discontinuation of study intervention are met. The total duration of treatment is up to approximately 16 months.
干预措施: Intismeran autogene (Biological)
Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery
Participants will receive neoadjuvant treatment with up to 4 cycles of pembrolizumab plus EV and 1 to 4 doses of intismeran autogene, followed by radical cystectomy [RC] plus pelvic lymph node dissection [PLND], and then adjuvant treatment with up to 13 cycles of pembrolizumab plus up to 5 cycles of EV and 5 to 8 doses of intismeran autogene (for a total of 9 neoadjuvant plus adjuvant Intismeran autogene doses), or until any of the protocol-specified criteria for discontinuation of study intervention are met. The total duration of treatment is up to approximately 16 months.
干预措施: Enfortumab Vedotin (Biological)
Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery
Participants will receive neoadjuvant treatment with up to 4 cycles of pembrolizumab plus EV and 1 to 4 doses of intismeran autogene, followed by radical cystectomy [RC] plus pelvic lymph node dissection [PLND], and then adjuvant treatment with up to 13 cycles of pembrolizumab plus up to 5 cycles of EV and 5 to 8 doses of intismeran autogene (for a total of 9 neoadjuvant plus adjuvant Intismeran autogene doses), or until any of the protocol-specified criteria for discontinuation of study intervention are met. The total duration of treatment is up to approximately 16 months.
干预措施: Surgery (RC plus PLND) (Procedure)
结局指标
主要结局
Adjuvant Cohort: Disease Free Survival (DFS)
时间窗: Up to approximately 28 months
DFS is defined as the time from randomization until death from any cause, or presence of disease per investigator assessment with muscle-invasive (≥pT2) disease or any high-grade non-muscle invasive disease in the urothelial tract (upper tract or lower tract) on imaging and biopsy, and/or disease recurrence outside the urothelial tract on imaging with or without confirmation by biopsy. DFS will be reported for the Adjuvant Cohort.
Perioperative Cohort: Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 19 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience AEs will be reported for the Perioperative Cohort.
Perioperative Cohort: Number of Participants Who Discontinue Study Treatment Due to AE
时间窗: Up to approximately 16 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinue study treatment due to an AE will be reported for the Perioperative Cohort.
次要结局
- Adjuvant Cohort: Overall Survival (OS)(Up to approximately 28 months)
- Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)(Up to approximately 28 months)
- Adjuvant Cohort: Number of Participants Who Experience an AE(Up to approximately 16 months)
- Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 13 months)
- Perioperative Cohort: Pathologic Complete Response (pCR) Rate(Up to approximately 18 weeks)
- Perioperative Cohort: Pathologic Downstaging (pDS) Rate(Up to approximately 18 weeks)