A Clinical Study of Intismeran Autogene (V940) and BCG in People With Bladder Cancer (V940-011/INTerpath-011)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

Conditions: Urinary Bladder Neoplasms; Carcinoma in Situ; Non-Muscle Invasive Bladder Neoplasms

Treatments: Biological: Intismeran autogene; Biological: BCG

Study type: Interventional

Funder types: Industry

Identifiers

NCT06833073

2024-517335-46-00 (EU Trial (CTIS) Number)

U1111-1312-0572 (Other Identifier)

INTerpath-011 (Other Identifier)

V940-011 (Other Identifier)

Details and patient eligibility

About

Researchers are looking for new ways to treat people with high-risk non-muscle invasive bladder cancer (HR NMIBC). NMIBC is cancer in the tissue that lines the inside of the bladder but has not spread to the bladder muscle or outside of the bladder. High-risk means NMIBC may have a high chance of getting worse or coming back after treatment. HR NMIBC can also include carcinoma in situ (CIS). CIS is bladder cancer that appears flat and is only in the inner layer (surface) of the bladder. CIS is not raised and is not growing toward the center of the bladder.

The standard treatment for HR NMIBC is a procedure to remove the tumor called transurethral resection of the bladder tumor (TURBT) followed by Bacillus Calmette-Guerin (BCG). Standard treatment is something that is considered the first line of treatment for a condition. BCG is an immunotherapy, which is a treatment that helps the immune system fight cancer. However, BCG may not work to treat HR NMIBC in some people. Researchers want to learn if adding intismeran autogene, the study treatment, to standard treatment can help treat HR NMIBC. Intismeran autogene is designed to help a person's immune system attack their specific cancer.

The goal of this study are to learn if people who receive V940 with BCG live longer and without the cancer growing, spreading, or coming back compared to people who receive BCG alone.

Full description

As of Amendment 03 (effective 01/05/2026), outcome measures associated with the Intismeran autogene Monotherapy Arm (Cohort B) are no longer considered primary or secondary outcome measures.

Enrollment: 308 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:

- Is an individual whose most recent TURBT was performed within 12 weeks before randomization/allocation and showed BICR-confirmed high-risk NMIBC histology

Cohort A:

• Has high-risk non-muscle invasive (HG Ta, T1, and/or CIS) UC of the bladder
• Is BCG-naïve defined as either having never received BCG or having received BCG more than 2 years before high-risk NMIBC recurrence. Recurrence must be at least 24 months from the last exposure to BCG with evidence of complete response during the 2-year period post BCG

Cohort B:

• Has CIS +/-papillary non-muscle invasive UC of the bladder
• Is ineligible for, or refusing, any IVESIC therapy
• Is either BCG-naïve (as defined above) or BCG-exposed but did not receive protocol-specified minimum dosing of BCG and experienced recurrence of high-risk NMIBC within 2 years of the last dose of BCG
• Human immunodeficiency virus (HIV)-infected individuals must have well controlled HIV on antiretroviral therapy (ART)

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

• Has a history of or concurrent locally-advanced (ie, T2, T3, T4) or metastatic UC
• Has concurrent extravesical (ie, urethra, ureter, renal pelvis) non-muscle invasive UC or a history of extravesical non-muscle invasive UC that recurred within the last 2 years, with certain exceptions
• Has a known additional malignancy that is progressing or has required active treatment within the last 3 years
• Has had a myocardial infarction within 6 months of randomization/allocation
• Has received any systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation
• Has received prior treatment with a cancer vaccine
• Has immunodeficiency or is receiving chronic systemic steroid therapy
• Has active autoimmune disease that has required systemic treatment in the last 2 years
• Has any contraindication to IV contrast and gadolinium or is otherwise unable to have imaging with either computerized tomography urogram (CTU) or Magnetic resonance urography (MRU)

Cohort A:

• Has current active tuberculosis
• Has a known history of HIV infection

Cohort B:

- HIV-infected individuals with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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308 participants in 3 patient groups

Intismeran autogene + BCG

Experimental group

Description:

Participants in Cohort A receive 1 mg of intismeran autogene via intramuscular (IM) injection every 3 weeks (Q3W) for 9 doses. Participants also receive 50 mg of TICE® BCG once weekly for 6 weeks, then once weekly on weeks 13-15, 25-27, 49-51, and 73-75.

Treatment:

Biological: BCG

Biological: Intismeran autogene

BCG

Active Comparator group

Description:

Participants in Cohort A receive 50 mg of TICE® BCG once weekly for 6 weeks, then once weekly on weeks 13-15, 25-27, 49-51, and 73-75.

Treatment:

Biological: BCG

Intismeran autogene

Experimental group

Description:

Participants in Cohort B receive 1 mg of intismeran autogene via intramuscular (IM) injection every 3 weeks (Q3W) for 9 doses.

Treatment:

Biological: Intismeran autogene