D090 Bladder Bladder
Conditions
Interventions
V940 as injection, solution, with unit dose concentration of 1 mg/ml. 1 mg will be administered intramuscularly every 3 weeks for 9 cycles. And Pembrolizumab as Injection, solution, concentrate with u
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male Participants: No contraception measures are required for participants capable of producing sperm Type of Participant and Disease Characteristics: The participant must have MIUC originating in the lower tract (bladder, urethra) or upper tract (renal pelvis, ureter). NOTE: UTUC enrollment will be capped at 20%. Type of Participant and Disease Characteristics: Dominant histology must be UC. Histology will be determined locally. • Participants with mixed histology are eligible provided the urothelial component is =50%. • Participants whose tumors contain any neuroendocrine component are not eligible. Type of Participant and Disease Characteristics: Participants must have undergone radical resection for MIUC =8 weeks before providing informed consent and =16 weeks before randomization. Radical resection refers to radical nephroureterectomy (for upper tract MIUC) or radical cystectomy with pelvic lymph node dissection per AUA/ASCO/ASTRO/SUO guidelines. Partial cystectomy may be permitted upon Sponsor consultation. • Participants with positive surgical margins for microscopic disease (R1) are eligible. Type of Participant and Disease Characteristics: Participants must have high-risk pathologic disease (determined locally) after radical resection, as per 1 of 2 definitions: • For participants who received cisplatin-based neoadjuvant chemotherapy: ypT2-4a and/or ypN+ • For participants who have not received cisplatin-based neoadjuvant chemotherapy: pT3-4a and/or pN+ Type of Participant and Disease Characteristics: Participants who have not received cisplatin-based neoadjuvant chemotherapy are eligible with 1 of following scenarios: • Participant is cisplatin-ineligible per 1 or more of the following criteria: o CrCl (using the Cockcroft-Gault formula): 30 mL/min o CTCAE v5.0 Grade 2 or higher audiometric hearing loss o CTCAE v5.0, Grade 2 or higher peripheral neuropathy o ECOG performance status 2 • Participant is cisplatin-eligible but declines adjuvant cisplatin-based chemotherapy. Type of Participant and Disease Characteristics: Participants must provide an FFPE tumor tissue sample that is suitable for the NGS required for this study. NOTE: Tissue from the radical resection is mandated for participants who received neoadjuvant chemotherapy followed by radical resection. For participants who did not receive neoadjuvant chemotherapy and underwent radical resection, tissue from radical resection is strongly preferred to ensure QC for NGS is successful, but tissue from TURBT is allowed as long as tissue requirements are met. The tumor tissue sample must meet the following criteria: • Meet the minimum standards for tissue quantity and quality as defined in the laboratory manual. • Pass the required QC checks for NGS by the Sponsor’s NGS vendor. Type of Participant and Disease Characteristics: Participants must provide blood samples as specified in the protocol, to enable V940 production, and ctDNA testing. Type of Participant and Disease Characteristics: Participants must be disease-free (N0M0) with no evidence of disease per investigator assessment based on imaging studies within 4 weeks before randomization. • Imaging must include CT or MRI of the chest, abdomen, and pelvis. • For participants with upper tract disease and an intact bladder, a cystoscopy (with or without biopsy) must be performed within 4 weeks before randomization. • If there is clinical suspicion of CNS disease at screening, brain scan is required within 4
Exclusion criteria
Exclusion criteria: Prior/Concomitant Therapy: Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). Exception includes participants who received anti-PD-1 or PD-L1 therapy for NMIBC with recurrence >12 months before study randomization. Prior/Concomitant Therapy: Received prior systemic anticancer therapy including investigational agents in the adjuvant setting after radical surgery. Prior/Concomitant Therapy: Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to Section 6.5 for information on COVID-19 vaccines. Prior/Concomitant Therapy: Received therapy with hematopoietic growth factor such as G-CSF or GM-CSF within 14 days before randomization. Prior/Concomitant Therapy: Received prior treatment with a cancer vaccine. Prior/Concomitant Therapy: Prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy as stated in inclusion criterion #11. Prior/Concurrent Clinical Study Experience: Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnostic Assessments: Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication. Diagnostic Assessments: Known additional malignancy that is progressing or has required active treatment =3 years prior to study randomization. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk earlystage prostate cancer (T1-T2a, Gleason score =6, and PSA <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded. Diagnostic Assessments: Severe hypersensitivity (=Grade 3) to either V940 or pembrolizumab and/or any of their excipients. Diagnostic Assessments: Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed. Diagnostic Assessments: History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Diagnostic Assessments: Active infection requiring systemic therapy. Diagnostic Assessments: HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease. Diagnostic Assessments: Concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless: • Known history of HBV and HCV infection • As mandated by local health authority (See Appendix 7 for country-specific requirements) Diagnostic Assessments: History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Imaging and biopsy. NAME OF THE RESULT: Primary Efficacy Endpoint: Disease-Free Survival (DFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization until death from any cause or the presence of disease with the following characteristics, as assessed by the investigator: a) muscle-invasive disease (=pT2) in the urothelium (upper or lower tracts) or high-grade T1 disease in the upper tract, AND/OR b) recurrence of the disease outside the urothelium. | — |
Secondary
| Measure | Time frame |
|---|---|
| Imaging and biopsy. NAME OF THE RESULT: Primary Efficacy Endpoint: Disease-Free Survival (DFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization until death from any cause or the presence of disease with the following characteristics, as assessed by the investigator: a) muscle-invasive disease (=pT2) in the urothelium (upper or lower tracts) or high-grade T1 disease in the upper tract, AND/OR b) recurrence of the disease outside the urothelium.;Elapsed time NAME OF THE RESULT: Secondary Efficacy Endpoint: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to death from any cause.;Imaging and biopsy NAME OF THE RESULT: Secondary Efficacy Endpoint: Distant Metastasis-free Survival (DMFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to death from any cause or disease recurrence outside the urothelium, according to the investigator's assessment.;Clinical review of all relevant parameters, including AEs, laboratory test results, and vital signs. NAME OF THE RESULT: Safety and tolerability PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The measurement of each parameter will be carried out according to the schedule described in the protocol. | — |
Countries
Australia, Canada, Chile, Colombia, France, Germany, Italy, Korea South, New Zealand, Peru, Poland, Spain, Sweden, Turkey, United Kindgdom
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed