Bladder cancer drug combo trial halted early – what we know

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histologically confirmed transitional cell urothelial carcinoma. Participants with mixed histologies are required to have a dominant (ie, 50% at least) transitional cell pattern. * Clinical stage T2-T3b, N0, M0 muscle invasive urothelial carcinoma by CT (or MRI) (Stage II-IIIA per AJCC 2018) * Refuse cisplatin therapy (does not apply in France) or are ineligible for cisplatin therapy per modified Galsky criteria with exclusion of Eastern Cooperative Oncology Group( ECOG) PS 2 participants * Eligible for radical cystectomy * Eastern Cooperative Oncology Group (ECOG) Performance Status( PS) 0 or 1. * Pretreatment tumor biopsy must be a tumor block or 20 unstained slides from biopsy of primary tumor containing at least 20% tumor. * Willingness to avoid pregnancy or fathering children from screening through 100 days in the US and 190 days in Europe after the last dose of study drug Exclusion Criteria: * Participation in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) before first dose. * Previously received systemic therapy for bladder cancer or received prior treatment with checkpoint inhibitor agents (such as anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4). * Evidence of measurable nodal or metastatic disease. * Concurrent anticancer therapy. * Has had major surgery within 4 weeks before enrollment (C1D1). * Has had known additional malignancy other than muscle-invasive Urothelial Bladder Cancer ( miUBC) that is progressing or requires active treatment, along with some protocol exceptions, or history of other malignancy within 2 years of study entry, with some predefined-protocol exceptions. * Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (\> 10 mg daily doses of prednisone or equivalent) or immunosuppressive drugs within 2 years of Day 1 of study treatment. * Participants with laboratory values outside of protocol defined ranges. * Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent). * Has a known active hepatitis B (defined as HBsAg and total anti-HBc positive results) or hepatitis C (HCV Ab positive result and HCV RNA \>LLoD) or HIV,HBV, HCV or hepatitis virus coinfection. * Participants with HIV+ disease along with protocol defined exceptions that don't have undetectable viral load along with other protocol exceptions. * Has known carcinomatous meningitis. * Active infection requiring systemic antibiotics ≤ 14 days from first dose of study drug. * Participants with known or suspected active COVID-19 infection. * Use of probiotics within 28 days from first dose of study drug. * Current use of prohibited medication as per protocol. * Has not recovered to ≤ Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention. * History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval \> 450 milliseconds is excluded. * History of a gastrointestinal condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) that may affect oral drug absorption. * Has received a live vaccine within 30days of planned start of study therapy * Participants with impaired cardiac function or clinically significant cardiac disease * Prior allogenic tissue/solid organ transplant * Evidence of interstitial lung disease or active, noninfectious pneumonitis. * Has known hypersensitivity to any of the study drugs, excipients, including mannitol or another monoclonal antibody which cannot be controlled with standard measures (eg, antihistamines and corticosteroids). * Any ≥ Grade 2 immune-related toxicity while receiving prior immunotherapy. * History of serotonin syndrome after receiving 1 or more serotonergic drugs. * Concomitant use of medications that are known to be substrates of CYP1A2, CYP2C8, or CYP2C19 with narrow therapeutic window are prohibited (see Section 6.6.3). * Patients who are receiving or required to receive medications that are known to be UGT1A9 inhibitors (see Section 6.6.3).