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
Overview
- Phase
- Phase 2
- Intervention
- retifanlimab
- Conditions
- Urothelial Carcinoma
- Sponsor
- Incyte Corporation
- Enrollment
- 30
- Locations
- 12
- Primary Endpoint
- Change From Baseline in CD8+ Lymphocytes Within the Resected Tumor
- Status
- Terminated
- Last Updated
- 6 months ago
Overview
Brief 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.
Detailed Description
Participants will be stratified based on Programmed cell Death-Ligand 1 (PD-L1) Combined Positive Score ( CPS) \< 10 and PD-L1 CPS ≥ 10.
Investigators
Eligibility 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) (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
- •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.
Arms & Interventions
Treatment Group A
epacadostat will be administered in combination with retifanlimab.
Intervention: retifanlimab
Treatment Group A
epacadostat will be administered in combination with retifanlimab.
Intervention: epacadostat
Treatment Group B
retifanlimab will be administered as monotherapy.
Intervention: retifanlimab
Treatment Group C
epacadostat will be administered as monotherapy.
Intervention: epacadostat
Treatment Group D
retifanlimab will be administered in combination with INCAGN02385.
Intervention: retifanlimab
Treatment Group D
retifanlimab will be administered in combination with INCAGN02385.
Intervention: INCAGN02385
Treatment Group E
retifanlimab will be administered in combination with INCAGN02385 and INCAGN02390.
Intervention: retifanlimab
Treatment Group E
retifanlimab will be administered in combination with INCAGN02385 and INCAGN02390.
Intervention: INCAGN02385
Treatment Group E
retifanlimab will be administered in combination with INCAGN02385 and INCAGN02390.
Intervention: INCAGN02390
Outcomes
Primary Outcomes
Change From Baseline in CD8+ Lymphocytes Within the Resected Tumor
Time Frame: up to 69 days
Fold Change from Baseline in CD8+ lymphocytes = CD8+ Lymphocytes at cystectomy divided by CD8+ lymphocytes at Screening. Translational data in all but the retifanlimab 500 mg Q4W treatment group were limited and insufficient to assess this outcome measure.
Secondary Outcomes
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE)(up to 159 days)
- Number of Participants With Any ≥Grade 3 TEAE(up to 159 days)
- Pathological Complete Response Rate(up to 69 days)
- Major Pathological Response(up to 69 days)