SASANLIMAB for Non-muscle invasive bladder cancer | Bladder cancer

Inclusion criteria

• {"criterion_text":"- Written informed consent stating that he/she understands the purpose of the study and the procedures involved and agrees to participate in the study.\n- Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures\n- Histological confirmed diagnosis of BCG-unresponsive high-risk, nonmuscle invasive urothelial carcinoma obtained via Transurethral resection of bladder tumour (TURBT) no later than 16 weeks prior to screening visit, defined as: a. Persistent or recurrent CIS alone or with recurrent high-grade Ta/T1 (non-invasive papillary disease/tumour invades the subepithelial connective tissue) disease within 16 months of completion of adequate BCG therapy. b. Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy. c. T1 high-grade disease at the first evaluation following an induction BCG. Patients should be allowed to enrol in the study even if more time has elapsed and/or if patient has tried another agent meantime since BCG unresponsiveness was established (on the basis that these situations do not change biology of the disease that initially classified the patient as BCG unresponsive).\n- Have refused or are ineligible for radical cystectomy\n- Pure or predominant (≥50%) urothelial carcinoma (UC) histology as determined at the local site.\n- Age ≥ 18 years.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n- Adequate organ function prior to Cycle 1 Day 1, as specified below: a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without granulocyte colony stimulating factor (GCSF) support); platelet count ≥ 100 x 109/L; haemoglobin ≥ 9 g/dL without transfusion within 1-week preceding study drug administration; b. International normalized ratio (INR) or Prothrombin time (PT) ≤1.5 x upper limit of normal (ULN); c. Hepatic: total bilirubin ≤ 1.5 x ULN, transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/GOT and alanine aminotransferase/serum glutamic pyruvic transaminaseALT/GPT) ≤ 2.5 x ULN; d. Creatinine clearance ≥30 mL/min based either on Cockcroft-Gault estimate or based on urine collection (24 hour).\n- No other malignancy (diagnosis within the last 2 years), except for adequately treated non-melanoma skin cancer (basal or squamous) and carcinoma in situ of cervix.\n- Willingness to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 6 months after the last dose of study drugs, unless confirmed to be azoospermic (vasectomized or secondary to medical cause). Males must also refrain from donating sperm for the purposes of assisted reproduction during the same time-period. b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 6 months after the last dose of study drugs. Women of nonchildbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy or ≥ 12 months of amenorrhea) are eligible. Females must also refrain from donating egg (ovum) for the purposes of assisted reproduction during the same time period."}

Exclusion criteria

• {"criterion_text":"- Evidence of muscle-invasive, locally advanced, or metastatic urothelial cancer or concurrent UC in upper urinary tracts (ureters or renal pelvis).\n- Uncontrolled adrenal insufficiency\n- True positive test results for active hepatitis B or C during screening.\n- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).\n- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure (NyHA>class II), unstable angina pectoris cardiac arrhythmia requiring medication except for atrial fibrillation that is rate controlled with medication, myocardial infarction within 6 months of Cycle 1 Day 1, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.\n- Known allergy or hypersensitivity to study drug formulations.\n- Known history of allergy to protein-based therapies or a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anaemia).\n- Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.\n- Has a 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 14 days prior to the first dose of study drug.\n- Has an active autoimmune disease that has required systemic treatment in the past 6 months (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.\n- Pregnancy or breastfeeding.\n- Involvement of the prostatic urethra or invasive prostatic transitional cell carcinoma including T1 or greater disease.\n- Any systemic or intravesical chemotherapy or immunotherapy from the time of most recent positive TURBT (confirming BCG-unresponsive high-risk, non-muscle invasive urothelial carcinoma) to initiation of study intervention. Intravesical chemotherapy treatment given as part of the most recent cystoscopy/TURBT as per local/regional practices, is acceptable. Limited intravesical chemo is acceptable after discussing with the sponsor.\n- Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody\n- Prior treatment with immunostimulatory agents including interleukin (IL)-2, IL-15, interferon (INF).\n- Prior radiation therapy to the bladder.\n- Has tumour with any percentage of neuroendocrine or small cell component.\n- Major surgical procedure within 28 days prior to the first dose or still recovering from prior surgery. Port placement or any type of central venous placement is not considered major. The same as for biopsy procedures.\n- Severe infection within 2 weeks of the first use of study drug."}

Primary endpoints

• {"endpoint_text":"- Complete Response (CR) Rate of high-grade disease at 3 months (defined as the absence of high-risk disease or progressive disease, assessed by cystoscopy and urine cytology, and biopsy (when applicable)","definition_or_measurement_approach":"Defined as the absence of high-risk disease or progressive disease, assessed by cystoscopy and urine cytology, and biopsy (when applicable)."}

Secondary endpoints

• {"endpoint_text":"- Adverse events (AEs).","definition_or_measurement_approach":"Safety assessed by recording adverse events (AEs)."}
• {"endpoint_text":"- CR rate of high-risk disease at 6, 12, 18 and 24 months.","definition_or_measurement_approach":"Complete response assessed at 6, 12, 18 and 24 months (same assessment approach as primary: cystoscopy, urine cytology, biopsy when applicable)."}
• {"endpoint_text":"- Median duration of complete response (DOR) in patients with a Complete response (CR).","definition_or_measurement_approach":"Duration measured from time of first documented CR until documented recurrence or progression."}
• {"endpoint_text":"- Progression-free survival (PFS) to worsening of grade, stage (muscle invasive or metastatic disease) or death.","definition_or_measurement_approach":"Time to worsening of grade or stage (progression to muscle-invasive or metastatic disease) or death."}
• {"endpoint_text":"- Overall Survival (OS).","definition_or_measurement_approach":"Time from study entry to death from any cause."}
• {"endpoint_text":"- 6-month, 12-month, 18-month and 24-month OS and PFS to worsening of grade, stage (muscle-invasive or metastatic disease) or death.","definition_or_measurement_approach":"OS and PFS rates estimated at 6, 12, 18 and 24 months."}

Spain

Earliest CTIS Part Ii Submission Date

23-10-2024

Latest Decision Or Authorization Date

10-09-2025

Processing Time Days

322

Number Of Sites

20

Number Of Participants

42

Primary sponsor

Full Name

Associacio Per A La Recerca Oncologica

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain

Contract research organisations

Name

Pivotal S.L.

Responsibilities

Operational and regulatory duties as listed in sponsorDuties codes: 1,10,11,12,15 (Pharmacovigilance),2,5,6,7,8; contact pivotalregulatoryunit@pivotalcr.com

Third parties

• {"country":"Spain","full_name":"Parc Tauli Hospital Universitari","duties_or_roles":"Codes: 15 (Plasma and urine ctDNA analysis), 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Pivotal S.L.","duties_or_roles":"Codes: 1, 10, 11, 12, 15 (Pharmacovigilance), 2, 5, 6, 7, 8; contact email: pivotalregulatoryunit@pivotalcr.com","organisation_type":"Pharmaceutical company"}