An Umbrella Study to Determine the Safety and Efficacy of Various Monotherapy or Combination Therapies in Neoadjuvant Urothelial Carcinoma

Trial details

Who runs it

Incyte Corporation

Trial code

NCT04586244

Record updated

2025. október 30.

Original description

This is a multicenter, open-label, randomized, Phase 2 umbrella study of various neoadjuvant treatment combinations in participants who have muscle-invasive urothelial carcinoma of the bladder and are cisplatin-ineligible or refusing cisplatin therapy and awaiting radical cystectomy.Read full original descriptionShow less

An Open-Label, Randomized, Phase 2, Umbrella Study to Investigate the Biological Rational of Various Neoadjuvant Therapies for Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Cisplatin-Ineligible or Refuse Cisplatin Therapy and Undergoing Radical Cystectomy

This is a multicenter, open-label, randomized, Phase 2 umbrella study of various neoadjuvant treatment combinations in participants who have muscle-invasive urothelial carcinoma of the bladder and are cisplatin-ineligible or refusing cisplatin therapy and awaiting radical cystectomy.

Inclusion: 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: 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); Concurrent anticancer therapy; Has had major surgery within 4 weeks before enrollment (C1D1); 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; Has received a live vaccine within 30days of planned start of study therapy; Prior allogenic tissue/solid organ transplant; 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); Evidence of measurable nodal or metastatic disease; 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; 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; Active infection requiring systemic antibiotics ≤ 14 days from first dose of study drug; Participants with known or suspected active COVID-19 infection; History of a gastrointestinal condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) that may affect oral drug absorption; Participants with impaired cardiac function or clinically significant cardiac disease; 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); Participants with laboratory values outside of protocol defined ranges; Has known carcinomatous meningitis; History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 450 milliseconds is excluded.

ClinicalTrials.gov NCT04586244