D090 Bladder Bladder
Conditions
Interventions
V940 as 1 mg/ml injection. 1 mg will be administered IM every 3 weeks for 9 cycles. TICE® BCG as powder for suspension 50 mg (wet weight). 1 vial will be administered by intravesical instillation. Ind
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Type of Participant and Disease Characteristics 1. Cohort A: Is an individual with a BICR-confirmed histological diagnosis of high-risk non-muscle invasive (HG Ta, T1, and/or CIS) UC of the bladder. Note: Individuals with unifocal HG Ta =3 cm alone are not eligible. Cohort B: Is an individual with a BICR-confirmed histological diagnosis of CIS +/- papillary non-muscle invasive UC of the bladder and is ineligible for, or refusing, any IVESIC therapy. Note: Individuals who have HG Ta or T1 without CIS are not eligible. Note: Ineligibility for, or refusal of, I-VESIC therapy must be clearly recorded in the source documents. If ineligible for I-VESIC therapy, the cause of ineligibility must be documented. Cohorts A and B: - Confirmation of T1 stage requires the presence of detrusor muscle in the tumor tissue. - Individuals with tumors of mixed histology are eligible provided the conventional urothelial component is =50%. - Individuals whose tumors contain any neuroendocrine or small cell component are not eligible. Type of Participant and Disease Characteristics 2. Is an individual whose most recent TURBT was performed within 12 weeks before randomization/allocation and showed BICR-confirmed high-risk NMIBC histology as detailed in Inclusion Criterion #1. For individuals with papillary tumors (Ta and T1), a complete TURBT must have been performed, as characterized by attainment of a visually complete resection of all papillary tumors (Ta and T1). Note: Individuals with residual CIS not amenable to complete resection are eligible. Note: Individuals with T1 disease must have undergone a restaging TURBT procedure within 12 weeks before randomization/allocation confirming complete resection and that the individual continues to meet eligibility criteria. Individuals who undergo restaging TURBT of BICR T1 lesion(s) are still eligible if the restaging TURBT: - Is performed within 12 weeks before randomization/allocation even if the previous TURBT was performed >12 weeks before randomization/allocation; - Is BICR-confirmed as absent of muscle-invasive tumor (=T2) with or without a highrisk NMIBC diagnosis. Tumor samples from the most recent TURBT available before randomization/allocation, which includes the diagnostic and any restaging TURBT, as applicable, must be sent to the central pathology laboratory to confirm eligibility before randomization/allocation. Type of Participant and Disease Characteristics 3. Cohort A: 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: Is either BCG-naïve (as defined above) or BCG-exposed who did not receive adequate dosing of BCG and experienced recurrence of high-risk NMIBC within 2 years of the last dose of BCG. Adequate dosing is defined as at least: - 5 of 6 doses of induction; and - 2 of 3 doses of the first maintenance cycle or 2 of 6 doses of a second induction. Demographics 4. Is an individual of any sex/gender who is at least 18 years of age at the time of providing documented informed consent. Assigned Male Sex at Birth Note: There are no contraceptive requirements for individuals assigned male sex at birth. Assigned Female Sex at Birth 5. A participant assigned female sex at birth is eligible to participate if not breastfeeding during the study intervention period and for at l
Exclusion criteria
Exclusion criteria: Medical Conditions 5. HIV-infected individuals with a history of Kaposi’s sarcoma and/or multicentric Castleman’s Disease. Medical Conditions 1. Has a history of or concurrent locally-advanced (ie, T2, T3, T4) or metastatic UC. Medical Conditions 2. 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. - Individuals with concurrent LG Ta of the prostatic urethra are eligible. - Individuals with prostatic ductal invasion regardless of histology are not eligible. Medical Conditions 3. Has a known additional malignancy that is progressing or has required active treatment within the last 3 years. Note: Individuals with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, who have undergone potentially curative therapy are eligible. Note: Individuals with a history of prostate cancer (T2N0M0 or lower with a Gleason score =7) that was treated with definitive intent (surgically or through radiation therapy) at least 1 year before study entry are eligible, provided they are considered prostate cancer disease free and the following criteria are met: i) individuals who underwent radical prostatectomy must have an undetectable PSA for >1 year and during the screening period; and ii) individuals treated with radiation must have a PSA doubling time >1 year (based on at least 3 values taken more than one month apart) and a total PSA that does not meet Phoenix criteria for biochemical recurrence (ie, PSA must be 1 year (based on at least 3 values taken more than one month apart) are also eligible. Medical Conditions 4. Has had a myocardial infarction within 6 months of randomization/allocation. Prior/Concomitant Therapy 6. Has received any systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation. Note: Intravesical chemotherapy treatment given as part of the most recent cystoscopy/TURBT per local/regional practices is acceptable. Note: All AEs due to previous therapies must have recovered to Grade =1 or baseline. Note: Individuals must have recovered adequately from the toxicity and/or complications of major surgery before randomization/allocation. Prior/Concomitant Therapy 7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live-attenuated vaccines and are not allowed. Note: Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed in the study as long as it is an mRNA vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. These vaccines will be treated just as any other concomitant therapy. Note: No vaccine should be administered within 10 days before the first dose of V940. Note: Since the first dose of study intervention in Cohort B may not be received within the time periods specified in this criterion, eligibility for individuals in Cohort B must be confirmed at the time of screening and reverified before the first dose of V940. Prior/Concomitant Therapy 8. Has received prio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Events are determined by BICR using urine cytology, biopsy, and radiologic assessments, using point estimates and CIs with the exact binomial method. NAME OF THE RESULT: Complete response rate (CRR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first occurrence of any of the defined events.;Events are determined by BICR, as measured by the stratified log-rank test, estimated by the stratified Cox model with the Efron method for handling ties. NAME OF THE RESULT: Event-Free Survival (EFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first occurrence of any of the defined events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Events are determined by BICR using urine cytology, biopsy, and radiologic assessments, using point estimates and CIs with the exact binomial method. NAME OF THE RESULT: Complete response rate (CRR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first occurrence of any of the defined events.;Proportion of participants with EFS within 12 months of randomization NAME OF THE RESULT: 12-month EFS Rate – Cohort A PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At 12 months from randomization;Proportion of participants with EFS within 24 months of randomization NAME OF THE RESULT: 24-month EFS Rate – Cohort A PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At 24 months from randomization;Events are determined by BICR, as measured by the stratified log-rank test, estimated by the stratified Cox model with the Efron method for handling ties. NAME OF THE RESULT: Event-Free Survival (EFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first occurrence of any of the defined events.;Measures the time from the first dose of study intervention to the first occurrence of: (1) Any event included in the definition of EFS (2) Any other UC recurrence, including LG Ta at any time, as well as HG Ta or bladder CIS prior to the 24-week assessment NAME OF THE RESULT: Recurrence-free Survival (RFS) - Cohort A PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Occurrence of any of the defined events.;Measures the time from randomization to death from bladder cancer. NAME OF THE RESULT: Disease-specific Survival (DSS) - Cohort A PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: When death from bladder cancer | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, Denmark, France, Germany, Greece, Hungary, Italy, Nederland, Peru, Poland, Spain, Thailand, United Kindgdom, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed