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

NCT04586244 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: INCB 24360-9012020-002244-23
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 12

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.

Conditions

Urothelial Carcinoma

Keywords

Muscle-invasive cisplatin-ineligible; urothelial carcinoma of the bladder; radical cystectomy.; epacadostat; retifanlimab; TIM-3; LAG-3

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in CD8+ Lymphocytes Within the Resected Tumor

  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.

  up to 69 days

Secondary Outcomes (4)

• 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

Study Arms (5)

Treatment Group A

EXPERIMENTAL

epacadostat will be administered in combination with retifanlimab.

Drug: retifanlimab; Drug: epacadostat

Treatment Group B

EXPERIMENTAL

retifanlimab will be administered as monotherapy.

Drug: retifanlimab

Treatment Group C

EXPERIMENTAL

epacadostat will be administered as monotherapy.

Drug: epacadostat

Treatment Group D

EXPERIMENTAL

retifanlimab will be administered in combination with INCAGN02385.

Drug: retifanlimab; Drug: INCAGN02385

Treatment Group E

EXPERIMENTAL

retifanlimab will be administered in combination with INCAGN02385 and INCAGN02390.

Drug: retifanlimab; Drug: INCAGN02385; Drug: INCAGN02390

Interventions

retifanlimab 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 A; Treatment Group B; Treatment Group D; Treatment Group E

epacadostat DRUG

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

Treatment Group A; Treatment Group C

INCAGN02385 DRUG

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

Treatment Group D; Treatment Group E

INCAGN02390 DRUG

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

Treatment Group E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (12)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Ohio State University Medical Center Division of H

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-4501, United States

Location

Hopital Europeen Georges Pompidou (Hegp)

Paris, 75015, France

Location

Hospital Saint Louis

Paris, 75475, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari

Bari, 70124, Italy

Location

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

Bologna, 40138, Italy

Location

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

Milan, 20132, Italy

Location

Universita Campus Bio Medico Di Roma

Roma, 00128, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

Verona, 37124, Italy

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

epacadostat

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

The sponsor made a strategic decision to stop further enrollment of participants in cohorts encompassing epacadostat in clinical studies. The sponsor later made a strategic decision (not based on safety concerns) to stop enrollment in all treatment groups, and the study was subsequently terminated.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Diane Hershock, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 14, 2020
• Study Start: January 14, 2022
• Primary Completion: January 29, 2024
• Study Completion: January 29, 2024
• Last Updated: October 30, 2025
• Results First Posted: March 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.

Locations

US (4); FR (3); IT (5)