neoadjuvant toripalimab in combination with gemcitabine and cisplatin therapy in local advanced bladder cancer subjects

Conditions: Urinary Bladder Cancer

Summary: this is a pre-surgical study involving subjects with local advanced bladder cancer, who are candidates for neoadjuvant therapy. it is a single-arm phase ii portion.

outline: this study is a single-arm, open, exploratory clinical trial; subjects receive: gemcitabine 1000mg/m2 iv day1 and day8 every 21 days repeated for 4 cycles; cisplatin 35mg/m2 iv day1 and day2 every 21 days, repeated for 4 cycles. toripalimab at recommended phase ii dose is given every 3 weeks for 4 doses starting with cycle1 day1(c1d1). subjects will then have surgery to remove their primary tumor within 6 weeks after their last dose of neoadjuvant therapy. eastern cooperative oncology group (ecog) performance status: 0-1 demonstrate adequate organ function as defined by the following laboratory values at study entry. all screening labs should be performed within 28 days of c1d1. hematopoetic: absolute neutrophil count (anc) ≥1,500 /mcl absolute lymphocyte count ≥350 mcl platelets ≥100,000 / mcl hemoglobin ≥9 g/dl or ≥5.6 mmol/l renal: measured or calculated creatinine clearance ≥30 ml/min hepatic: serum total bilirubin ≤ 1.25 x uln or ≤ 2.5 x uln for subjects with gilbert's disease aspartate aminotransferase (ast, sgot) and alanine aminotransferase (alt, sgpt) ≤ 2 x uln coagulation: international normalized ratio (inr) or prothrombin time (pt) ≤1.5 x uln unless subject is receiving anticoagulant therapy as long as pt or ptt is within therapeutic range of intended use of anticoagulants activated partial thromboplastin time (aptt) ≤1.5 x uln unless subject is receiving anticoagulant therapy and as long as pt or ptt is within therapeutic range of intended use of anticoagulants

Eligibility criteria:
inclusion criteria: * patients between 18 and 75 years old on day of signing informed consent, regardless of gender; * ecog score 0-1 points, expected survival time\> 6 months; * pathologically confirmed locally advanced bladder urothelial carcinoma (ct2-t4a, n≤1, m0, tumor staging according to american joint committee on cancer (ajcc), 2017, eighth edition); * appropriate and plan for radical cystectomy; * according to the recist1.1 standard, there is at least one measurable lesion (spiral ct scan ≥10mm); * since the diagnosis of locally advanced bladder urothelial carcinoma, patient has not received anti-tumor system treatment; * the main organ functions are normal, and the following requirements must be met within 2 weeks before the first study treatment: * routine blood examination must meet: wbc≥4.0×109/l; plt≥90×109/l; hb≥90g/l (patients can be infused with red blood cells to meet this standard); * blood biochemical examination must meet: serum creatinine (cr) ≤1.5 times the upper limit of normal (uln) or endogenous creatinine clearance ≥60ml/min; tbil≤1.5×uln; alb≥30g/l; alt and ast≤ 3.0×uln; tsh≤1.5×uln. * female patients with fertility must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and they voluntarily adopt appropriate methods of contraception during the observation period and within 8 weeks after the last administration; * agree to provide diagnosis and treatment-related tumor tissue specimens for clinical research, and have the ability to follow the planned research visit until the clinical recurrence/progress is clear. * sign informed consent voluntarily. exclusion criteria: * have previously received anti-pd1/pdl1/ctla-4 antibody treatment or systemic chemotherapy, bladder infusion chemotherapy is excluded; * have received bladder bacille calmette guerin (bcg) infusion therapy within 4 weeks; * have received radiotherapy of the bladder in the past; * patients with any history of active autoimmune disease or autoimmune disease; * complicated diseases that require the use of immunosuppressive drugs; concurrent diseases that require the use of immunosuppressive agents for systemic or locally absorbable corticosteroids. it is forbidden to use prednisone greater than 10 mg/day or the same dose in the 2 weeks before the use of the study drug; * combined with other malignant tumors; * have a history of allergy to other antibody drugs; * the history of human immunodeficiency virus (hiv) infection; * the subject has active infection, including active tuberculosis; * combined with severe heart disease, or combined with new york heart association (nyha) grade 3 or 4 cardiac insufficiency; * kidney transplant patients;

Keywords: bladder cancer checkpoint inhibitor neoadjuvant therapy