Clinical trial NCT06833073: A Clinical Study of Intismeran Autogene (V940) and BCG in People With Bladder Cancer (V940-011/INTerpath-011)
Official title: A Phase 2 Open-label Randomized Study of V940 in Combination With BCG Versus BCG Monotherapy in Participants With High-risk Non-muscle Invasive Bladder Cancer (INTerpath-011)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Non-Muscle Invasive Bladder Neoplasms
Carcinoma in Situ
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: ModernaTX, Inc.
First posted: 2025-02-18
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants allocated to receive BCG will be randomized 1:1 to the intismeran autogene+BCG arm and the BCG arm.

Participants allocated to receive intismeran autogene monotherapy will be allocated to the single intismeran autogene monotherapy arm.
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: BCG Arms: Event-free Survival (EFS)
timeFrame: Up to approximately 5 years
measure: Intismeran autogene Monotherapy Arm: Complete Response Rate (CRR)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: BCG Arms: 12-Month Event-free Survival (EFS)
timeFrame: Up to approximately 12 months
measure: BCG Arms: 24-Month Event-free Survival (EFS)
timeFrame: Up to approximately 24 months
measure: Recurrence-free Survival (RFS)
timeFrame: Up to approximately 5 years
measure: Disease-specific Survival (DSS)
timeFrame: Up to approximately 5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: BCG Arms: 12 Month Overall Survival Rate (OSR)
timeFrame: Up to approximately 12 months
measure: BCG Arms: 24 Month Overall Survival Rate (OSR)
timeFrame: Up to approximately 24 months
measure: BCG Arms: Complete Response Rate (CRR)
timeFrame: Up to approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Time to Cystectomy
timeFrame: Up to approximately 5 years
measure: Intismeran autogene Monotherapy Arm: 6-Month CRR
timeFrame: Up to approximately 6 months
measure: Intismeran autogene Monotherapy Arm: 12-Month CRR
timeFrame: Up to approximately 6 months
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 21 months
measure: Number of Participants Who Discontinue Study Intervention Due to an AE
timeFrame: Up to approximately 18 months
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Michael G Oefelein Clinical Trials ( Site 0138)
state: California
city: Los Alamitos
country: United States
facility: Los Alamitos Hematology Oncology Medical Group ( Site 0141)
state: California
city: Torrance
country: United States
facility: Genesis Healthcare-Torrance ( Site 0140)
state: California
city: Torrance
country: United States
facility: Genesis Research LLC ( Site 0118)
state: California
city: Hialeah
country: United States
facility: Urological Research Network ( Site 0133)
state: Florida
city: Columbia
country: United States
facility: University of Missouri Health Care ( Site 0126)
state: Missouri
city: Lincoln
country: United States
facility: NHO Revive Research Institute, LLC ( Site 0137)
state: Nebraska
city: Portland
country: United States
facility: OHSU Knight Cancer Institute - South Waterfront ( Site 0110)
state: Oregon
city: Austin
country: United States
facility: Urology Austin, PLLC ( Site 0109)
state: Texas
city: Virginia Beach
country: United States
facility: Urology of Virginia ( Site 0125)
state: Virginia
city: Buenos Aires
country: Argentina
facility: Asociación de Beneficencia Hospital Sirio Libanés ( Site 0303)
state: Caba
city: Rosario
country: Argentina
facility: Fundacion Estudios Clinicos ( Site 0304)
state: Santa Fe
city: Rosario
country: Argentina
facility: Sanatorio Parque ( Site 0300)
state: Santa Fe
city: La Rioja
country: Argentina
facility: Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0301)
city: Macquarie University
country: Australia
facility: Macquarie University ( Site 1801)
state: New South Wales
city: Arnhem
country: Netherlands
facility: Rijnstate ( Site 1307)
state: Gelderland
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos... ( Site 1500)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena ( Site 1504)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: