AzTrials
AzTrials

Urothelial CarcinomaPhase 2OptimusNCT04586244

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

A Phase 2 study testing retifanlimab, epacadostat and INCAGN02385 in people with Urothelial Carcinoma, run by Incyte Corporation at 12 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
retifanlimab, epacadostat and INCAGN02385
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
12 sitesin 3 countries
Study dates
14 Jan 2022to 29 Jan 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 28Show fewer
  • 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).

Trial locations and contacts

12 sites in 3 countries.

12 sites in 3 countries

Italy5 sites

  • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari

    Bari, 70124

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

    Bologna, 40138

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

    Milan, 20132

  • Universita Campus Bio Medico Di Roma

    Roma, 00128

  • Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

    Verona, 37124

Other trials in Italy

United States4 sites

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Ohio State University Medical Center Division of H

    Columbus, Ohio, 43210

  • University of Iowa

    Iowa City, Iowa, 52242

  • Oregon Health & Science University

    Portland, Oregon, 97239-4501

Other trials in United States

France3 sites

  • Hopital Europeen Georges Pompidou (Hegp)

    Paris, 75015

  • Hospital Saint Louis

    Paris, 75475

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
retifanlimab, epacadostat, INCAGN02385, INCAGN02390
Keywords
Muscle-invasive cisplatin-ineligible, urothelial carcinoma of the bladder, radical cystectomy., epacadostat, retifanlimab, TIM-3, LAG-3
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • retifanlimabDrug

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

  • epacadostatDrug

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

  • INCAGN02385Drug

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

  • INCAGN02390Drug

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

Study groups in NCT04586244
Study groupRoleWhat they receive
Treatment Group AExperimentalepacadostat will be administered in combination with retifanlimab.
Receives: Drug: retifanlimab; Drug: epacadostat
Treatment Group BExperimentalretifanlimab will be administered as monotherapy.
Receives: Drug: retifanlimab
Treatment Group CExperimentalepacadostat will be administered as monotherapy.
Receives: Drug: epacadostat
Treatment Group DExperimentalretifanlimab will be administered in combination with INCAGN02385.
Receives: Drug: retifanlimab; Drug: INCAGN02385
Treatment Group EExperimentalretifanlimab will be administered in combination with INCAGN02385 and INCAGN02390.
Receives: Drug: retifanlimab; Drug: INCAGN02385; Drug: INCAGN02390

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 69 days

Secondary outcomes (4)

  1. Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

    An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

    Measured: up to 159 days

  2. Number of Participants With Any ≥Grade 3 TEAE

    An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

    Measured: up to 159 days

  3. Pathological Complete Response Rate

    Pathological complete response rate was defined as the percentage of participants with ypT0N0.

    Measured: up to 69 days

  4. Major Pathological Response

    Major pathological response was defined as the percentage of participants with residual ypT0/1/a/isN0M0.

    Measured: up to 69 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2020
  2. Study start14 Jan 2022
  3. Primary completion29 Jan 2024
  4. Study completion29 Jan 2024

Why it stopped: Business Decision. No safety concerns contributed to this decision.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04586244
Sponsor's protocol ID
INCB 24360-901
Other IDs
2020-002244-23
Acronym
Optimus
Status last verified
Oct 2025
First submitted
8 Oct 2020
Last updated
30 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing retifanlimab, epacadostat and INCAGN02385 in people with Urothelial Carcinoma, run by Incyte Corporation at 12 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Italy, United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in CD8+ Lymphocytes Within the Resected Tumor (time frame: up to 69 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04586244.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2025; AzTrials last refreshed its copy on 6 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in