A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Bladder Cancer

Treatments: Biological: Intismeran autogene; Biological: Enfortumab Vedotin; Other: Placebo; Biological: Pembrolizumab; Procedure: Surgery (RC plus PLND)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06305767

U1111-1292-1952 (Other Identifier)

V940-005 (Other Identifier)

2023-505658-17-00 (Registry Identifier)

INTerpath-005 (Other Identifier)

Details and patient eligibility

About

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.

Full description

Enrollment of participants into the Phase 1 Perioperative Cohort of this study is planned to start in approximately April of 2025.

Enrollment: 230 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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 MIUC
• 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:

• Has MIBC
• 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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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230 participants in 3 patient groups

Adjuvant Cohort: Pembrolizumab + Intismeran autogene

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab

Biological: Intismeran autogene

Adjuvant Cohort: Pembrolizumab + Placebo

Active Comparator group

Description:

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.

Treatment:

Biological: Pembrolizumab

Other: Placebo

Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery

Experimental group

Description:

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.

Treatment:

Procedure: Surgery (RC plus PLND)

Biological: Pembrolizumab

Biological: Enfortumab Vedotin

Biological: Intismeran autogene