A Prospective, Multi-Center, Phase 4, Single Arm Study To Assess The Safety and Tolerability of Perioperative Durvalumab in Combination With Neoadjuvant Gemcitabine Plus Cisplatin in Indian Patients With Muscle-Invasive Bladder Cancer Cle-Invasive

• Durvalumab (Drug), also known as IMFINZI: Solution for IV infusion, 1500 mg/vial. Administered at 1500 mg IV every 3 weeks during the neoadjuvant phase and every 4 weeks during the adjuvant phase.
• Gemcitabine (Drug): Solution for IV infusion. Administered at 1000 mg/m² on Day 1 and Day 8 of each 21-day neoadjuvant cycle.
• Cisplatin (Drug): Solution for IV infusion. Administered at 70 mg/m² on Day 1 of each 21-day neoadjuvant cycle. A split dose of 35 mg/m² on Days 1 and 8 may be used for patients with borderline renal function.

Primary outcomes

• Number of subjects experiencing adverse events (AEs) [Throughout the study, up to approximately 66 weeks]: The number of subjects experiencing adverse events (AEs), with categorization of AEs by system organ class, preferred term, and CTCAE grade.

Secondary outcomes

• Incidence of Treatment-Emergent Adverse Events (TEAEs) and Adverse Drug Reactions (ADRs) [Throughout the study, up to approximately 66 weeks]: Percentage of Subjects with SAEs, TEAEs \& with ADRs during the study.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* * Participant must be ≥18 years of age inclusive.
* * Patients with histologically or cytologically documented muscle-invasive TCC (also known as UC) of the bladder.
* * Patients with transitional cell and mixed transitional/non-transitional cell histologies.
* * Patients with clinical tumour stage T2-T4aN0/1M0.
* * Medically fit for treatment with neoadjuvant therapy prior to radical cystectomy.
* * Medically fit to undergo a radical cystectomy at time of enrolment.
* * Have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC.
* * Body weight >30 kg.
* * Male participants must use a condom plus an additional contraceptive method.
* * Female participants must be postmenopausal or have evidence of nonchildbearing status.
* * Capable of giving signed informed consent.
* * Must have a life expectancy of at least 12 weeks at Enrollement.
* * Adequate bone marrow function (Haemoglobin ≥ 9.0 g/dL, Absolute neutrophil count ≥ 1.5 × 10\^9/L, Platelet count ≥100 x 10\^9/L).
* * Adequate renal function (Creatinine clearance (CrCL) > 40 mL/min).
* * Adequate hepatic function (Total bilirubin ≤ 1.5 × ULN, AST and ALT ≤2.5 x ULN).

Exclusion Criteria:

* * Evidence of lymph node (N2-3) or metastatic TCC/UC (M1), extravesical TCC/UC (T4b), or primary non-bladder TCC/UC.
* * Any unresolved toxicity Grade ≥2 from previous anticancer therapy except for alopecia, vitiligo, and specified laboratory values.
* * Major surgical procedure within 2 weeks of starting study treatment.
* * Requirement for a nephroureterectomy at the time of enrollement for tumour of the mid ureter, renal pelvis, or collecting system.
* * Inoperable tumour(s) with fixation to the pelvic wall on clinical exam.
* * History of allogeneic organ transplantation that requires use of immunosuppressive agents.
* * Active or previously documented autoimmune or inflammatory disorders.
* * Uncontrolled intercurrent illness.
* * History of another primary malignancy, with exceptions.
* * Resting ECG indicating uncontrolled, potentially reversible cardiac conditions.
* * History of active primary immunodeficiency.
* * History of a myocardial infarction within 6 months prior to enrollement.
* * Any clinically significant systemic disease or medical condition that could interfere with the study.
* * Any clinically significant systemic disease or medical condition that could interfere with the study.
* * HIV positive.
* * Any medical contraindication to platinum (Cisplatin)-based doublet chemotherapy.
* * Concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment.
* * Prior exposure to immune-mediated therapy (with exclusion of BCG).
* * Current or prior use of immunosuppressive medication within 14 days before the first dose of Durvalumab, with exceptions.
* * Prior pelvic radiotherapy treatment within 2 years of enrollement to study.
* * Receipt of live attenuated vaccine within 30 days before the first dose of study treatment.
* * Concomitant use of known strong or moderate CYP3A inhibitors.
* * Concomitant use of known strong or moderate CYP3A inducers.
* * Participation in another clinical study with a study intervention administered in the last 30 days.
* * Involvement in the planning and/or conduct of the study.
* * Involvement in the planning and/or conduct of the study.
* * For females only - currently pregnant or breastfeeding.