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

Phase 2

Recruiting

• Conditions: Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Carcinoma in Situ
• Interventions: Biological: Intismeran autogene; Biological: BCG

• Registration Number: NCT06833073
• Lead Sponsor: Merck Sharp & Dohme LLC

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 goals of this study are to learn:

* If people who receive intismeran autogene with BCG live longer without the cancer growing, spreading, or coming back, or dying from any cause, compared to people who receive BCG alone

* If more people who receive intismeran autogene with BCG have their cancer go away (complete response), compared to people who receive BCG alone

* How many people who receive intismeran autogene without BCG have their cancer go away

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-04
• Study First Submitted QC: 2025-02-12
• Study First Posted: 2025-02-18
• Study Start: 2025-03-11
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-16
• Last Update Posted: 2025-07-17
• Primary Completion: 2031-09-03
• Study Completion: 2031-09-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 308

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

BCG Arms:

• 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

Intismeran autogene Monotherapy Arm:

• 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)

BCG Arms:

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

Intismeran autogene Monotherapy Arm:

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intismeran autogene + BCG	Intismeran autogene	Participants 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.
Intismeran autogene + BCG	BCG	Participants 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.
BCG	BCG	Participants 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.
Intismeran autogene	Intismeran autogene	Participants receive 1 mg of intismeran autogene via intramuscular (IM) injection every 3 weeks (Q3W) for 9 doses.

Primary Outcome Measures

Name	Time	Method
BCG Arms: 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) where applicable: 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 \[defined as regional lymph node metastasis of UC (stage N1 or greater), or distant lymph node or visceral metastasis of UC (stage M1)\]; Or death due to any cause. The EFS for BCG-treated participants will be presented.
Intismeran autogene Monotherapy Arm: 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 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 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 \[defined as regional lymph node metastasis of UC (N1 or greater), or distant lymph node or visceral metastasis of UC (M1)\]. The CRR for intismeran autogene monotherapy-treated participants will be presented.

Secondary Outcome Measures

Name	Time	Method
BCG Arms: 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.
BCG Arms: 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.
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.
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.
Overall Survival (OS)	Up to approximately 5 years	OS is defined as the time from randomization to death due to any cause.
BCG Arms: 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.
BCG Arms: 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.
BCG Arms: 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 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 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 \[defined as regional lymph node metastasis of UC (N1 or greater), or distant lymph node or visceral metastasis of UC (M1)\]. The CRR for BCG-treated participants will be presented.
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 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 \[defined as regional lymph node metastasis of UC (N1 or greater), or distant lymph node or visceral metastasis of UC (M1)\]), 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.
Time to Cystectomy	Up to approximately 5 years	Time to cystectomy, defined as the time from randomization to the date of cystectomy, will be presented for BCG-treated participants.
Intismeran autogene Monotherapy Arm: 6-Month CRR	Up to approximately 6 months	6-month CRR is defined as the percentage of participants who achieve a CR (defined as 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 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 \[defined as regional lymph node metastasis of UC (N1 or greater), or distant lymph node or visceral metastasis of UC (M1)\]) by 6 months starting from the first dose of study intervention. The 6-month CRR for intismeran autogene-treated participants will be presented.
Intismeran autogene Monotherapy Arm: 12-Month CRR	Up to approximately 6 months	12-month CRR is defined as the percentage of participants who achieve a CR (defined as 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 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 \[defined as regional lymph node metastasis of UC (N1 or greater), or distant lymph node or visceral metastasis of UC (M1)\]) by 6 months starting from the first dose of study intervention. The 12-month CRR for intismeran autogene-treated participants will be presented.
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.
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.

Trial Locations

Locations (45)

Michael G Oefelein Clinical Trials ( Site 0138); 🇺🇸 Bakersfield, California, United States

Genesis Research, LLC ( Site 0141); 🇺🇸 Los Alamitos, California, United States

USC Norris Comprehensive Cancer Center ( Site 0123); 🇺🇸 Los Angeles, California, United States

Genesis Healthcare-Torrance ( Site 0140); 🇺🇸 Torrance, California, United States

Genesis Research LLC ( Site 0118); 🇺🇸 Torrance, California, United States

Urological Research Network ( Site 0133); 🇺🇸 Hialeah, Florida, United States

Associated Urological Specialists - Chicago Ridge ( Site 0139); 🇺🇸 Chicago Ridge, Illinois, United States

University of Missouri Health Care ( Site 0126); 🇺🇸 Columbia, Missouri, United States

NHO Revive Research Institute, LLC ( Site 0137); 🇺🇸 Lincoln, Nebraska, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0111); 🇺🇸 New York, New York, United States

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