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

• Status: Not yet recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Incyte Corporation

Criteria

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) + Positron Emission Tomography (PET)/CT (Stage II-IIIA per American Joint Committee on Cancer (American Joint Committee on Cancer (AJCC) 2018)).

• Ineligible for cisplatin therapy per modified Galsky criteria with exclusion of Eastern Cooperative Oncology Group( ECOG) PS 2 participants

• Participants who refuse cisplatin-based therapy.

• Eligible for radical cystectomy

• Residual disease after TURBT (eg, surgical opinion, cystoscopy or radiological presence).

• 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

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.

• 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 range.

• 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 (HBsAg reactive) or hepatitis C or HIV,HBV, HCV or hepatitis virus coinfection.

• Participants with HIV+ disease 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 COVID-19 infection.

• Use of probiotics within 28 days from first dose of study drug.

• Current use of prohibited medication as per protocol.

• History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.

• 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