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

NCT ID: NCT04586244

Last Updated: 2025-10-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-14
• Study Completion Date: 2024-01-29

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.

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Group A

epacadostat will be administered in combination with retifanlimab.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,

epacadostat

Intervention Type: DRUG

epacadostat will be administered daily twice daily orally up to and including day of surgery.

Treatment Group B

retifanlimab will be administered as monotherapy.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,

Treatment Group C

epacadostat will be administered as monotherapy.

Group Type: EXPERIMENTAL

epacadostat

Intervention Type: DRUG

epacadostat will be administered daily twice daily orally up to and including day of surgery.

Treatment Group D

retifanlimab will be administered in combination with INCAGN02385.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,

INCAGN02385

Intervention Type: DRUG

INCAGN02385 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.

Treatment Group E

retifanlimab will be administered in combination with INCAGN02385 and INCAGN02390.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,

INCAGN02385

Intervention Type: DRUG

INCAGN02385 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.

INCAGN02390

Intervention Type: DRUG

INCAGN02390 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.

Interventions

retifanlimab

retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,

Intervention Type: DRUG

epacadostat

epacadostat will be administered daily twice daily orally up to and including day of surgery.

Intervention Type: DRUG

INCAGN02385

INCAGN02385 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.

Intervention Type: DRUG

INCAGN02390

INCAGN02390 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.

Intervention Type: DRUG

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 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Diane Hershock, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

University of Iowa

Iowa City, Iowa, United States

University of Cincinnati

Cincinnati, Ohio, United States

Ohio State University Medical Center Division of H

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Hopital Europeen Georges Pompidou (Hegp)

Paris, , France

Hospital Saint Louis

Paris, , France

Institut Gustave Roussy

Villejuif, , France

Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari

Bari, , Italy

L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi

Bologna, , Italy

Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele

Milan, , Italy

Universita Campus Bio Medico Di Roma

Roma, , Italy

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

Verona, , Italy

Countries

United States; France; Italy

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-002244-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 24360-901

Identifier Type: -

Identifier Source: org_study_id