Bladder Preservation With Sacituzumab Govitecan + Zimberelimab for Muscle-Invasive Bladder Cancer

Inclusion Criteria: * Participant is at least 18 years old of age, at the time of providing informed consent. * The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention. * Patients deemed ineligible for Radical Cystectomy (RC) + Retroperitoneal lymphnode dissection (RPNLD) by a urologist and/or oncologist and/or anesthesiology. * Cisplatin unfit patients as per Galsky criteria (ECOG Performance Status of 2 and/or creatinine-clearance \< 60 ml/min and/or CTCAE Gr ≥ 2 hearing loss and/or CTCAE Gr ≥ 2 neuropathy). * Cisplatin-fit patients are admitted if they are unwilling to undergo Radical Cystectomy (RC) and unwilling for cisplatin-based chemotherapy. * Patients deemed eligible for surgery will be included if they will be unwilling to undergo RC and will be ineligible and/or unwilling to cisplatin-based chemotherapy. * cT2-cT4 bladder cancer patients with predominant urothelial histology or Squamous cell histologic variant with histological confirmed diagnosis of muscle-invasive bladder cancer (MIBC) obtained via a diagnostic or maximal TURBT performed within 90 days before enrollment. * cN0-1 bladder cancer patients with predominant urothelial histology or Squamous cell histologic variant * Have adequate organ function as defined as follow (Specimens must be collected within 10 days prior to the start of study intervention): * Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study treatment initiations (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/μL). * Adequate hepatic function (bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN if known liver metastases, and serum albumin \> 3 g/dL). * Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation. * International normalized ratio (INR)/PT and PTT or aPTT ≤ 1.5 ULN unless patient is currently receiving therapeutic anticoagulant therapy. * Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease defined as: * Patients on ART must have a CD4+ T-cell count ≥ 350 cells/mm3 at time of screening. * Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening. * Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1). * The combination ART regimen must not contain any medications that may interfere with SN-38 metabolism. Exclusion Criteria: 1. Positive serum pregnancy test (Appendices 9.4) or women who are breastfeeding. 2. Known hypersensitivity to the study drug, its metabolites, or formulation excipient. 3. Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section. 4. Have had a prior anticancer biologic agent within 4 weeks prior to enrollment or have had prior chemotherapy or targeted small molecule therapy. Patients participating in observational studies are eligible. 5. Have previously received topoisomerase 1 inhibitors. 6. Have an active second malignancy. Note: patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll. Other exception are localized prostate cancer with a Gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence. 7. Patients with neuroendocrine histology will be excluded. 8. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment. 9. Have active serious infection requiring antibiotics. 10. Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism. 11. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded. * Patients who test positive for hepatitis B surface antigen (HBsAg). Patients who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease. * Patients who test positive for HCV antibody. Patients who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Patients with a known history of HCV or a positive HCV antibody test will not require a HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease. 12. Have 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. 13. Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the patient's participation in the study. 14. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug.