An Open Label, Single-arm, Phase 2 Study of Perioperative Sacituzumab Govitecan in Combination With Zimberelimab and Domvanalimab for Patients With Muscle Invasive Bladder Cancer Ineligible for Cisplatin-based Chemotherapy
The main objective of this trial is to evaluate the efficacy of the combo Sacituzumab govitecan (SG) + Zimberelimab (AB 122) (ZIM) + Domvanalimab (AB 154) (DOM), measured as pathologic complete response (pCR) rates, in the perioperative setting in patients with Muscle Invasive Bladder Cancer (MIBC) who are either unfit for platinum-based chemotherapy or unwilling to receive that therapy.
• Willing and able to provide written informed consent.
• Ability to comply with the study procedures and requirements and restrictions in this protocol.
• Age ≥ 18 years.
• Muscle invasive urothelial carcinoma stage cT2-T4cN0-1cM0. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) urothelial carcinoma pattern.
• Fit and planned for cystectomy (according to local guidelines).
• Refusal of neoadjuvant cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin-based therapy is not appropriate. (This will be determined by the investigator and not solely based in Galsky Criteria).
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site. Patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with the PI of the study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Adequate hematologic and end-organ function tests defined by the following:
∙ White Blood Cell (WBC) ≥ 2.0x109/L,
‣ Neutrophils ≥1.5x109/L,
‣ Platelets ≥100 x109/L,
‣ Hemoglobin ≥ 10 g/dL,
‣ Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation
‣ Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal(ULN),
‣ Alanine aminotransferase (ALT) ≤2.5 x ULN,
‣ Bilirubin ≤1.5 X ULN.
⁃ Adequate coagulation (Prothrombin Time \[PT\]) or International Normalized Ratio \[INR\] and Activated Partial Thromboplastin Time \[aPTT\]) ≤ 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.
⁃ Negative pregnancy test within 3 days of Day 1 Cycle 1 for female patients of childbearing potential.
⁃ Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.