Carcinoma in Situ, Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms
Conditions
Brief summary
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.
Detailed 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.
Interventions
BIOLOGICALIntismeran autogene
IM injection
BIOLOGICALBCG
Intravesicular instillation. BCG is a preparation of Bacillus Calmette-Guerin.
Sponsors
Merck Sharp & Dohme LLC
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants allocated to receive BCG will be randomized 1:1 to the intismeran autogene+BCG arm and the BCG arm (Cohort A). Participants allocated to receive intismeran autogene monotherapy will be allocated to the single intismeran autogene monotherapy arm (Cohort B).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: Event-free Survival (EFS) | Up to approximately 5 years | EFS is defined as the time from randomization to any of the following events, as determined by blinded independent central review (BICR): High-grade (HG) non-invasive papillary carcinoma (Ta) or carcinoma in situ (CIS) in the bladder at the 24-week assessment or later; Any T1 stage disease in the bladder; Any T2 stage or greater in the bladder, including transurethral prostate stromal invasion of urothelial carcinoma (UC); High-risk disease (defined as HG Ta, CIS, ≥T1) of the urethra or upper tract (ureters, renal pelvis); Metastatic UC \[defined as regional lymph node metastasis of UC (stage N1 or greater), or distant metastasis of UC including non-regional lymph nodes (stage M1)\]; Or death due to any cause. The EFS for BCG-treated participants will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: 12-Month Event-free Survival (EFS) | Up to approximately 12 months | EFS is defined as the time from randomization to any of the following events, as determined by BICR where applicable: HG Ta or CIS in the bladder at the 24-week assessment or later; Any T1 stage disease in the bladder; Any T2 stage or greater in the bladder, including transurethral prostate stromal invasion of UC; High-risk disease (defined as HG Ta, CIS, ≥T1) of the urethra or upper tract (ureters, renal pelvis); Metastatic UC \[defined as regional lymph node metastasis of UC (stage N1 or greater), or distant lymph node or visceral metastasis of UC (stage M1)\]; Or death due to any cause. The EFS at 12 months for BCG-treated participants will be presented. |
| Cohort A: 24-Month Event-free Survival (EFS) | Up to approximately 24 months | EFS is defined as the time from randomization to any of the following events, as determined by BICR where applicable: HG Ta or CIS in the bladder at the 24-week assessment or later; Any T1 stage disease in the bladder; Any T2 stage or greater in the bladder, including transurethral prostate stromal invasion of UC; High-risk disease (defined as HG Ta, CIS, ≥T1) of the urethra or upper tract (ureters, renal pelvis); Metastatic UC \[defined as regional lymph node metastasis of UC (stage N1 or greater), or distant lymph node or visceral metastasis of UC (stage M1)\]; Or death due to any cause. The EFS at 24 months for BCG-treated participants will be presented. |
| Cohort A: Recurrence-free Survival (RFS) | Up to approximately 5 years | RFS is defined as the time from randomization to any of the following events, as determined by BICR where applicable: HG Ta or CIS in the bladder at the 24-week assessment or later; Any T1 stage disease in the bladder; Any T2 stage or greater in the bladder, including transurethral prostate stromal invasion of UC; High-risk disease (defined as HG Ta, CIS, ≥T1) of the urethra or upper tract (ureters, renal pelvis); Metastatic UC \[defined as regional lymph node metastasis of UC (stage N1 or greater), or distant lymph node or visceral metastasis of UC (stage M1)\]; Death due to any cause; or any other UC recurrence including low-grade (LG) Ta at any timepoint as well as HG Ta or CIS in the bladder before the 24-week assessment. The RFS will be presented. |
| Cohort A: Disease-specific Survival (DSS) | Up to approximately 5 years | DSS is defined as the time from randomization to death due to bladder cancer. The DSS will be presented. |
| Cohort A: Overall Survival (OS) | Up to approximately 5 years | OS is defined as the time from randomization to death due to any cause. |
| Cohort A: 12 Month Overall Survival Rate (OSR) | Up to approximately 12 months | OSR is defined as the percentage of participants who are alive at 12 months. The 12 month OSR for BCG-treated participants will be presented. |
| Cohort A: 24 Month Overall Survival Rate (OSR) | Up to approximately 24 months | OSR is defined as the percentage of participants who are alive at 24 months. The 24 month OSR for BCG-treated participants will be presented. |
| Cohort A: Complete Response Rate (CRR) | Up to approximately 5 years | CRR is defined as the percentage of participants who achieve a Complete Response (CR) defined as the absence of all of the following as determined by BICR: High-risk non-muscle invasive UC (defined as HG Ta, CIS, or any T1 disease of the bladder, urethra, or upper tract \[ureters, renal pelvis\]); Any T2 or greater in the bladder, including transurethral prostate stromal invasion of UC; Metastatic UC \[defined as regional lymph node metastasis of UC (N1 or greater), or distant metastasis of UC including non-regional lymph nodes (M1)\]. The CRR for BCG-treated participants will be presented. |
| Cohort A: Duration of Response (DOR) | Up to approximately 5 years | For participants who achieve a Complete Response (CR: the absence of all of the following as determined by BICR using urine cytology, biopsy, and radiology assessments as applicable, and local cystoscopy evaluation: High-risk non-muscle invasive UC (defined as HG Ta, CIS, or any T1 UC in the bladder, urethra; Any T2 or greater UC in the bladder, including transurethral prostate stromal invasion of UC; Extravesical UC as defined in CR; Metastatic UC \[defined as regional lymph node metastasis of UC (N1 or greater), or distant lymph node or visceral metastasis of UC (M1)\]), DOR is defined as the time from first documented CR to the first occurrence of any of the following: High-risk non-muscle invasive UC; muscle-invasive bladder cancer (MIBC) or locally-advanced or metastatic UC; Or death due to any cause. DOR as assessed by BICR will be presented. |
| Cohort A: Time to Cystectomy | Up to approximately 5 years | Time to cystectomy, defined as the time from randomization to the date of radical cystectomy, will be presented for BCG-treated participants. |
| Cohort A: Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 21 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 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 intervention. The number of participants who experience an AE in the study will be presented. |
| Cohort A: Number of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately 18 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 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 intervention. The number of participants who discontinue the study intervention due to an AE in the study will be presented. |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Peru, Poland, Spain, Thailand, United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed