RELATLIMAB for Muscle-invasive bladder cancer (urothelial carcinoma), stage II–IIIa

Inclusion criteria

• {"criterion_text":"- Willing and able to provide informed consent\n- Negative pregnancy test (βHCG in blood or urine) within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.\n- Surgical resection (cystectomy) is the advised locoregional treatment and is accepted by the subject after consultation with the urologist.\n- Highly effective contraception for female subjects if the risk of conception exists. Female patients of childbearing potential must comply with contraception methods as requested by the study protocol (→ 8.2.1 Pregnancy, contraception and breastfeeding)\n- Age ≥ 18 years\n- Resectable muscle-invasive urothelial cancer of the bladder, defined as cT2-4aN0M0 OR cT1-4aN1M0. Note: in cT1N1 patients, lymph node positivity would need to be cytologically or histologically confirmed\n- Patients are either cisplatin ineligible or elect to not undergo cisplatin based neoadjuvant chemotherapy after a balanced discussion of risks and benefits with the treating physician. Cisplatin eligibility is determined based on the Galsky criteria\n- World Health Organization (WHO) performance Status 0 or 1\n- Urothelial cancer is the dominant histology (>50%). Any component of small cell of adenocarcinoma is not allowed\n- Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available.\n- Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.0x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, GFR>30 ml/min, AST ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN"}

Exclusion criteria

• {"criterion_text":"- Subjects with active autoimmune disease in the past 2 years. Patients with diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism, vitiligo, psoriasis or other mild skin disease can still be included.\n- Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated >10%). Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.\n- Pregnant and lactating female patients.\n- Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.\n- Severe infections within 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.\n- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias and unstable angina\n- Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).\n- Previous intravenous systemic therapy or radiotherapy for Urothelial cancer.\n- Upper urinary tract disease, unless all disease is planned to be resected in the same surgery as for Urothelial bladder cancer. This includes non-muscle-invasive disease.\n- Prior CTLA-4, LAG3 or PD-1/PD-L1-targeting immunotherapy.\n- Known active Human Immunodeficiency Virus infection, or tuberculosis, or other active infection: - HIV-positive patients are eligible if the following applies: \tNo AIDS defining opportunistic infection within the last year and a current CD4 count >350 cells/uL. \tReceived antiretroviral therapy (ART) for at least 4 weeks prior to treatment and continued while enrolled on study \tCD4 counts and viral load are monitored per standard of care by a local health care provider - In patients with a known history of hepatitis B or hepatitis C infection, Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA) should be negative\n- Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events. Examples may include severe pulmonary disease with extensive radiological abnormalities or intestinal disease causing severe diarrhea, not covered by other eligibility criteria, that may obscure colitis.\n- Medical condition requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) will be allowed.\n- Use of other investigational drugs before study drug administration"}

Primary endpoints

• {"endpoint_text":"- Pathological complete response (pCR), defined as pT0N0 or pTisN0, at cystectomy","definition_or_measurement_approach":"Defined in text as pT0N0 or pTisN0 at cystectomy"}

Secondary endpoints

• {"endpoint_text":"- Percentage of patients that completes cystectomy within 12 weeks of start of treatment. Patients who elect to not undergo surgery or have a delay due to logistical reasons not related to study treatment will be excluded from this analysis.","definition_or_measurement_approach":"Proportion of patients completing cystectomy within 12 weeks; exclusions applied for patient choice or non-treatment-related logistical delays"}
• {"endpoint_text":"- Overall Survival. Event-Free Survival; events are defined as: - Disease progression precluding surgery - Disease recurrence outside the urinary tract (distant metastases, pelvic recurrence) - Muscle invasive recurrence in the bladder or distal ureters - Switch to other treatments directed at systemic urothelial cancer","definition_or_measurement_approach":"Overall survival measured as time to death; Event-Free Survival with events defined as listed (disease progression precluding surgery; recurrence outside urinary tract; muscle-invasive recurrence in bladder or distal ureters; switch to other systemic treatments)"}
• {"endpoint_text":"- Immune-related adverse events (irAE) according to CTCAE 5.0 criteria","definition_or_measurement_approach":"Adverse events graded and categorized according to CTCAE v5.0"}

Netherlands

Earliest CTIS Part Ii Submission Date

21-12-2023

Latest Decision Or Authorization Date

07-05-2025

Processing Time Days

503

Number Of Sites

9

Number Of Participants

90

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"Bristol-Myers Squibb","duties_or_roles":"Source of monetary support","organisation_type":""}