DOMVANALIMAB for Muscle-invasive bladder cancer | Bladder cancer

Inclusion criteria

• {"criterion_text":"- Willing and able to provide written informed consent.\n- Adequate coagulation (Prothrombin Time [PT]) or International Normalized Ratio [INR] and Activated Partial Thromboplastin Time [aPTT]) ≤ 1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.\n- Negative pregnancy test within 3 days of Day 1 Cycle 1 for female patients of childbearing potential.\n- Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in annex 5\n- Ability to comply with the study procedures and requirements and restrictions in this protocol\n- Age ≥ 18 years.\n- Muscle invasive urothelial carcinoma of the bladder stage cT2-T4cN0- 1cM0. Patients with other histological subtypes [i.e. squamous, adenocarcinoma, etc] can also be included\n- Fit and planned for cystectomy (according to local guidelines)\n- Refusal of neoadjuvant cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin-based therapy is not appropriate. (This will be determined by the investigator and not solely based in Galsky Criteria)\n- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site. Patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with the PI of the study.\n- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.\n- Adequate hematologic and end-organ function tests defined by the following: a. WBC ≥ 2.0x109 /L, b. Neutrophils ≥1.5x109 /L, c. Platelets ≥100 x109 /L, d. Hemoglobin ≥ 10 g/dL, e. Creatinine clearance ≥ 30 mL/min as assessed by the CockcroftGault (https://www.mdcalc.com/calc/43/creatinine-clearance-cockcroftgaultequation) f. AST ≤ 2.5 x ULN, g. ALT ≤2.5 x ULN, h. Bilirubin ≤1.5 X ULN."}

Exclusion criteria

• {"criterion_text":"- Concurrent enrollment in another interventional clinical trial, unless in a follow-up period or it is an observational study.\n- Met any of the following criteria for cardiac disease: a. Myocardial infarction or unstable angina pectoris within 6 months of enrollment. b. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication). c. History of QT interval prolongation.\n- Patient currently on dialysis.\n- Gastrointestinal perforation within 6 months of enrollment.\n- Patients who have organ allografts\n- Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.\n- Known allergy or hypersensitivity to study drugs formulations.\n- Patients who have invasive catheters that under the investigator criteria might put the patient at risk of developing severe complications due to neutropenia [i.e. percutaneous nephrostomy\n- Females who are pregnant, lactating, or intend to become pregnant during their participation in the study.\n- 2. Having received previous anticancer therapy\n- Underlying medical conditions that might make the administration of study drugs hazardous or that might obscure the interpretation of adverse events\n- Patient receiving treatment with inhibitors or inducers of UGT1A1 at the time of enrollment.\n- Patient receiving treatment with high dose systemic corticosteroids (>10 mg of prednisone or its equivalent) within 2 weeks of C1D1.\n- Patients who have received a vaccination within 30 days prior to inclusion (examples include, but are not limited to, intranasal influenza vaccines, typhoid [oral] vaccines, and Bacillus Calmette-Guerin [BCG]). Patients are allowed to receive the COVID-19 vaccine to reduce the risk and complications of COVID-19 infection. The study visits should continue as planned if vaccination occurs while the patient is on the study.\n- Malignancy, other than bladder cancer, in the previous 2 years. Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) appropriately treated or that are treatment-naive and undergoing active surveillance are eligible. Also, noninvasive malignancies such as cervical carcinoma in situ, nonmelanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast, that have undergone potentially curative therapy are not excluded.\n- Major surgical procedure within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis or treatment of its bladder cancer\n- Severe infection within 4 weeks prior to enrollment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia."}

Primary endpoints

• {"endpoint_text":"- Efficacy of the combination of sacituzumab govitecan, zimberelimab and domvanalimab measured as pathologic complete response (pCR) rates. pCR is defined as absence of residual viable tumor (ypT0) in the radical cystectomy specimen and in the resected lymph nodes (ypN0) (posttreatment).","definition_or_measurement_approach":"pCR is defined as absence of residual viable tumor (ypT0) in the radical cystectomy specimen and in the resected lymph nodes (ypN0) (posttreatment)."}

Secondary endpoints

• {"endpoint_text":"- Efficacy of the combination of sacituzumab govitecan, zimberelimab and domvanalimab measured as the downstaging rates after neoadjuvant treatment. Downstaging is defined as any non-muscle invasive residual disease after treatment in the cystectomy specimen (i.e ypTis, ypTa, ypT1).","definition_or_measurement_approach":"Downstaging defined as any non-muscle invasive residual disease after treatment in the cystectomy specimen (i.e. ypTis, ypTa, ypT1)."}
• {"endpoint_text":"- Efficacy of neoadjuvant sacituzumab govitecan, zimberelimab and domvanalimab with respect to anti-tumor effects based on investigator assessed disease free survival (DFS). DFS event is defined as any of the following: development of distant metastasis of bladder carcinoma or presence of pelvic recurrence of bladder carcinoma (including soft tissue and regional lymph nodes) or death from any cause","definition_or_measurement_approach":"DFS event: development of distant metastasis of bladder carcinoma or pelvic recurrence (including soft tissue and regional lymph nodes) or death from any cause."}
• {"endpoint_text":"- Efficacy of neoadjuvant sacituzumab govitecan, zimberelimab and domvanalimab with respect to anti-tumor effects based on overall survival (OS). OS is defined as the time from informed consent signature to death from any cause.","definition_or_measurement_approach":"OS defined as time from informed consent signature to death from any cause."}
• {"endpoint_text":"- Safety and tolerability of the combination of sacituzumab govitecan, zimberelimab and domvanalimab measured as the incidence, nature and severity of adverse events (AEs).","definition_or_measurement_approach":"Measured as incidence, nature, and severity of adverse events (AEs)."}
• {"endpoint_text":"- Number of patients undergoing cystectomy later than 12 weeks after the last dose of sacituzumab govitecan, zimberelimab and domvanalimab treatment in the pre-operative setting.","definition_or_measurement_approach":"Count of patients undergoing cystectomy >12 weeks after last pre-operative dose."}
• {"endpoint_text":"- Cancer associated fibroblast (CAFs) as predictors of response. The differences in CAFs clusters (i.e. subpopulations) will be measured by scRNA seq and signatures analysis in responders vs non-responders, and assessed in combination with other clinical and molecular characteristics.","definition_or_measurement_approach":"Differences measured by single-cell RNA sequencing (scRNA-seq) and signature analyses comparing responders vs non-responders."}
• {"endpoint_text":"- Immune sub-populations as predictors of response","definition_or_measurement_approach":"Assessment of immune sub-populations (methods not further specified in record)."}
• {"endpoint_text":"- ctDNA as a predictor of benefit and marker of relapse.a. ct DNA levels will be measured at baseline, at the end of the neoadjuvant treatment before the cystectomy, after the cystectomy [at the beginning of the adjuvant phase], at the completion of the adjuvant treatment in the cohort assigned to this therapy, and thereafter every three months during follow-up visits for the first year (at weeks 16, 28, 40 and 52) in patients with pCR and negative ctDNA.","definition_or_measurement_approach":"ctDNA levels measured at baseline, end of neoadjuvant treatment (pre-cystectomy), post-cystectomy (start adjuvant), end of adjuvant (if assigned), then every 3 months during first year (weeks 16, 28, 40, 52) in patients with pCR and negative ctDNA."}
• {"endpoint_text":"- Efficacy of adjuvant zimberelimab and domvanalimab in a selected population [not pCR and/or +ctDNA] with respect to anti-tumor effects based on investigator assessed disease free survival (DFS). DFS event is defined as any of the following: development of distant metastasis of bladder carcinoma or presence of pelvic recurrence of urothelial carcinoma (including soft tissue and regional lymph nodes) or death from any cause.","definition_or_measurement_approach":"DFS event defined as distant metastasis, pelvic recurrence (including soft tissue and regional lymph nodes), or death from any cause."}
• {"endpoint_text":"- Efficacy of adjuvant zimberelimab and domvanalimab in a selected population [not pCR and/or +ctDNA] with respect to anti-tumor effects based on overall survival (OS). OS is defined as the time from informed consent signature to death from any cause.","definition_or_measurement_approach":"OS defined as time from informed consent to death from any cause."}

Spain

Earliest CTIS Part Ii Submission Date

17-03-2023

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

1089

Number Of Sites

10

Number Of Participants

70

Primary sponsor

Full Name

Fundacion Para El Progreso De La Oncologia En Cantabria

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Apices Soluciones S.L.","duties_or_roles":"sponsor duty codes: 1,10,11,12,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Logista Pharma S.A.","duties_or_roles":"Manufacturing and Import","organisation_type":"Pharmaceutical company"}