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Clinical Trial Results:
An Open-Label, Randomized, Phase 2, Umbrella Study 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 (Optimus)

Summary
EudraCT number	2020-002244-23
Trial protocol	FR IT
Global end of trial date	29 Jan 2024

Results information
Results version number	v1(current)
This version publication date	09 Feb 2025
First version publication date	09 Feb 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

INCB 24360-901

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Incyte Corporation

Sponsor organisation address

1801 Augustine Cutoff Drive, Wilmington, United States, 19803

Public contact

Study Director, Incyte Corporation, 1 855-463-3463, medinfo@incyte.com

Scientific contact

Study Director, Incyte Corporation, 1 855-463-3463, medinfo@incyte.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Oct 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Jan 2024

Was the trial ended prematurely?

Yes

Main objective of the trial

This study was conducted to determine biologic response in participants who had muscle-invasive urothelial carcinoma of the bladder and were cisplatin ineligible or refused cisplatin therapy and were awaiting radical cystectomy.

Protection of trial subjects

This study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws and country-specific regulations in which the study was being conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Jan 2022

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Italy: 16

Country: Number of subjects enrolled

United States: 9

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants were enrolled at 2 study centers in the United States, 2 study centers in Italy, and 1 study center in France.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Epacadostat 600 mg BID + retifanlimab 500 mg Q4W

Arm description

Participants received oral epacadostat 600 milligrams (mg) twice daily (BID) + intravenous retifanlimab 500 mg every 4 weeks (Q4W; on Day 1 of each 28-day cycle). Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Arm type

Experimental

Investigational medicinal product name

retifanlimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

25 mg/milliliter (mL) liquid formulation administered intravenously over 30 minutes (+ 15 minutes) on Day 1 of each 28-day cycle

Investigational medicinal product name

epacadostat

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

For the 600 mg BID dose, two 300-mg tablets BID. For the 400 mg BID dose reduction, one 300-mg and one 100-mg tablet. Both dose levels were administered without regard to food. Epacadostat was administered daily up to and including the day of surgery.

Retifanlimab 500 mg Q4W

Arm description

Participants received intravenous retifanlimab 500 mg Q4W (on Day 1 of each 28-day cycle). Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Arm type

Experimental

Investigational medicinal product name

retifanlimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

25 mg/mL liquid formulation administered intravenously over 30 minutes (+ 15 minutes) on Day 1 of each 28-day cycle

Epacadostat 600 mg BID

Arm description

Participants received oral epacadostat 600 mg BID. Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Arm type

Experimental

Investigational medicinal product name

epacadostat

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W

Arm description

Participants received intravenous retifanlimab 500 mg Q4W (on Day 1 of each 28-day cycle) + intravenous INCAGN02385 350 mg every 2 weeks (Q2W). Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Arm type

Experimental

Investigational medicinal product name

INCAGN02385

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

50 mg/mL administered intravenously (30-minute infusion with filter followed by flush)

Investigational medicinal product name

retifanlimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

25 mg/mL liquid formulation administered intravenously over 30 minutes (+ 15 minutes) on Day 1 of each 28-day cycle

Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg

Arm description

Participants received intravenous retifanlimab 500 mg Q4W (on Day 1 of each 28-day cycle) + intravenous INCAGN02385 350 mg Q2W + intravenous INCAGN02390 400 mg Q2W. Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Arm type

Experimental

Investigational medicinal product name

retifanlimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

25 mg/mL liquid formulation administered intravenously over 30 minutes (+ 15 minutes) on Day 1 of each 28-day cycle

Investigational medicinal product name

INCAGN02390

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

50 mg/ mL administered intravenously (30-minute infusion with filter followed by flush) every 2 weeks

Investigational medicinal product name

INCAGN02385

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

50 mg/mL administered intravenously (30-minute infusion with filter followed by flush) every 2 weeks

Number of subjects in period 1	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Started	3	20	2	4	1
Completed	2	19	2	3	1
Not completed	1	1	0	1	0
Lost to follow-up	1	-	-	1	-
AE Delayed Surgery; No Follow-Up Data Collected	-	1	-	-	-

Baseline characteristics

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Reporting group title

Epacadostat 600 mg BID + retifanlimab 500 mg Q4W

Reporting group description

Reporting group title

Retifanlimab 500 mg Q4W

Reporting group description

Reporting group title

Epacadostat 600 mg BID

Reporting group description

Participants received oral epacadostat 600 mg BID. Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Reporting group title

Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W

Reporting group description

Reporting group title

Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg

Reporting group description

Reporting group values	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg	Total
Number of subjects	3	20	2	4	1	30
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	0	5	1	0	0	6
From 65-84 years	3	15	1	4	1	24
85 years and over	0	0	0	0	0	0
Age Continuous
120=Mean (SD) age cannot be reported for a single participant due to privacy concerns.
Units: years
arithmetic mean (standard deviation)	75.7 ( 6.66 )	71.1 ( 6.08 )	65.0 ( 1.41 )	69.3 ( 3.86 )	120 ( 120 )	-
Sex/Gender, Customized
Units: participants
Female	0	2	1	1	0	4
Male	3	18	1	3	0	25
Cannot Be Reported Due to Participant Privacy	0	0	0	0	1	1
Race, Customized
Units: Subjects
White/Caucasian	2	16	2	4	0	24
Not Reported	1	4	0	0	0	5
Cannot Be Reported Due to Participant Privacy	0	0	0	0	1	1
Ethnicity, Customized
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0
Not Hispanic or Latino	2	15	1	4	0	22
Not Reported	1	5	1	0	0	7
Cannot Be Reported Due to Participant Privacy	0	0	0	0	1	1

End points

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Reporting group title

Epacadostat 600 mg BID + retifanlimab 500 mg Q4W

Reporting group description

Reporting group title

Retifanlimab 500 mg Q4W

Reporting group description

Reporting group title

Epacadostat 600 mg BID

Reporting group description

Participants received oral epacadostat 600 mg BID. Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Reporting group title

Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W

Reporting group description

Reporting group title

Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg

Reporting group description

Primary: Change from Baseline in CD8+ lymphocytes within the resected tumor

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End point title

Change from Baseline in CD8+ lymphocytes within the resected tumor ^[1]

End point description

Fold Change from Baseline in CD8+ lymphocytes = CD8+ Lymphocytes at cystectomy divided by CD8+ lymphocytes at Screening. Analysis was conducted in members of the Translation Evaluable Population, comprised of all participants who enrolled in the study who received at least 4 weeks of neoadjuvant study treatment (needed to receive the last dose of epacadostat within 2 days prior to the day of surgery or needed to receive the last dose of retifanlimab and/or INCAGN02385 and/or INCAGN02390 within the 7 weeks prior to day of surgery) and provided evaluable paired biopsies (pretreatment core biopsy and surgical resection biopsy). Translational data in all but the retifanlimab 500 mg Q4W treatment group were limited and insufficient to assess this outcome measure.

End point type

Primary

End point timeframe

up to 69 days

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not conducted for this endpoint.

End point values	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Number of subjects analysed	0 ^[2]	6 ^[3]	0 ^[4]	0 ^[5]	0 ^[6]
Units: log 2 of fold change
arithmetic mean (standard deviation)	( )	0.791 ( 0.9332 )	( )	( )	( )

Notes
[2] - Translation Evaluable Population
[3] - Translation Evaluable Population
[4] - Translation Evaluable Population
[5] - Translation Evaluable Population
[6] - Translation Evaluable Population

No statistical analyses for this end point

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

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End point title

Number of participants with any treatment-emergent adverse event (TEAE)

End point description

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. Analysis was conducted in members of the Safety Population, comprised of all participants who received at least 1 dose of study treatment. Treatment groups were determined according to the actual treatment the participant received regardless of the assigned study treatment.

End point type

Secondary

End point timeframe

up to 159 days

End point values	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Number of subjects analysed	3 ^[7]	20 ^[8]	2 ^[9]	4 ^[10]	1 ^[11]
Units: participants	3	18	2	4	1

Notes
[7] - Safety Population
[8] - Safety Population
[9] - Safety Population
[10] - Safety Population
[11] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with any ≥Grade 3 TEAE

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End point title

Number of participants with any ≥Grade 3 TEAE

End point description

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.

End point type

Secondary

End point timeframe

up to 159 days

End point values	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Number of subjects analysed	3 ^[12]	20 ^[13]	2 ^[14]	4 ^[15]	1 ^[16]
Units: participants	2	9	0	2	1

Notes
[12] - Safety Population
[13] - Safety Population
[14] - Safety Population
[15] - Safety Population
[16] - Safety Population

No statistical analyses for this end point

Secondary: Pathological complete response rate

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End point title

Pathological complete response rate

End point description

Pathological complete response rate was defined as the percentage of participants with ypT0N0. The 80% confidence interval was estimated using the Clopper-Pearson method. Analysis was conducted in members of the Efficacy Population, comprised of all participants with secondary efficacy endpoint data available for both Baseline and post-Baseline measurements.

End point type

Secondary

End point timeframe

up to 69 days

End point values	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Number of subjects analysed	2 ^[17]	20 ^[18]	2 ^[19]	4 ^[20]	1 ^[21]
Units: percentage of participants
number (confidence interval 80%)	100 (31.62 to 100)	40 (24.91 to 56.73)	0 (0 to 68.38)	0 (0 to 43.77)	100 (10 to 100)

Notes
[17] - Efficacy Population
[18] - Efficacy Population
[19] - Efficacy Population
[20] - Efficacy Population
[21] - Efficacy Population

No statistical analyses for this end point

Secondary: Major pathological response

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End point title

Major pathological response

End point description

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

End point type

Secondary

End point timeframe

up to 69 days

End point values	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Number of subjects analysed	2 ^[22]	20 ^[23]	2 ^[24]	4 ^[25]	1 ^[26]
Units: percentage of participants
number (confidence interval 80%)	100 (31.62 to 100)	50 (33.82 to 66.18)	50 (5.13 to 94.87)	50 (14.26 to 85.74)	100 (10 to 100)

Notes
[22] - Efficacy Population
[23] - Efficacy Population
[24] - Efficacy Population
[25] - Efficacy Population
[26] - Efficacy Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

up to 159 days

Adverse event reporting additional description

Adverse events have been reported for members of the Safety Population, comprised of all participants who received at least 1 dose of study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Epacadostat 600 mg BID + retifanlimab 500 mg Q4W

Reporting group description

Reporting group title

Retifanlimab 500 mg Q4W

Reporting group description

Reporting group title

Epacadostat 600 mg BID

Reporting group description

Participants received oral epacadostat 600 mg BID. Treatment continued for 4 to 10 weeks, as long as participants did not meet any criteria for study withdrawal.

Reporting group title

Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W

Reporting group description

Reporting group title

Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg

Reporting group description

Serious adverse events	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 3 (0.00%)	4 / 20 (20.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	1 / 1 (100.00%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Gastrointestinal disorders
Ileus paralytic
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myositis
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Postoperative wound infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Purulent discharge
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Epacadostat 600 mg BID + retifanlimab 500 mg Q4W	Retifanlimab 500 mg Q4W	Epacadostat 600 mg BID	Retifanlimab 500 mg Q4W + INCAGN02385 350 mg Q2W	Retifanlimab 500 mg + INCAGN02385 350 mg + INCAGN02390 400 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	18 / 20 (90.00%)	2 / 2 (100.00%)	4 / 4 (100.00%)	1 / 1 (100.00%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	4 / 20 (20.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	8	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 3 (33.33%)	3 / 20 (15.00%)	0 / 2 (0.00%)	3 / 4 (75.00%)	0 / 1 (0.00%)
occurrences all number	2	3	0	3	0
Asthenia
subjects affected / exposed	1 / 3 (33.33%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences all number	1	1	0	0	2
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	5 / 20 (25.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	7	1	0	1
Oedema peripheral
subjects affected / exposed	1 / 3 (33.33%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0
Hyperpyrexia
subjects affected / exposed	1 / 3 (33.33%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0
Reproductive system and breast disorders
Epididymal cyst
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Epididymal tenderness
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Testicular swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	1
Vaginal prolapse
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Vulvovaginal pruritus
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Cough
subjects affected / exposed	0 / 3 (0.00%)	2 / 20 (10.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	0	0
Atelectasis
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Amylase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Blood bicarbonate decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	0	0
Blood creatinine increased
subjects affected / exposed	1 / 3 (33.33%)	1 / 20 (5.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	1	1	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	2	0
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	1	0
C-reactive protein increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Carbon dioxide increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Inflammatory marker increased
subjects affected / exposed	0 / 3 (0.00%)	2 / 20 (10.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	3	0
Lipase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	1	0
Weight decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	1	0
Injury, poisoning and procedural complications
Post procedural discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Head injury
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Fall
subjects affected / exposed	0 / 3 (0.00%)	2 / 20 (10.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	0	0
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Nervous system disorders
Syncope
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	1 / 3 (33.33%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	1	0
Blood and lymphatic system disorders
Anemia
subjects affected / exposed	1 / 3 (33.33%)	5 / 20 (25.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	1 / 1 (100.00%)
occurrences all number	2	8	0	7	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	1	0
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Dry mouth
subjects affected / exposed	1 / 3 (33.33%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	1	0
Constipation
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	2	0
Anal incontinence
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Aerophagia
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0
Abdominal pain
subjects affected / exposed	0 / 3 (0.00%)	3 / 20 (15.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	4	0	1	0
Diarrhea
subjects affected / exposed	1 / 3 (33.33%)	1 / 20 (5.00%)	1 / 2 (50.00%)	3 / 4 (75.00%)	0 / 1 (0.00%)
occurrences all number	1	4	1	3	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 3 (33.33%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	5	1	0	0	0
Pruritus
subjects affected / exposed	0 / 3 (0.00%)	2 / 20 (10.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	0	0
Rash erythematous
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	1	0	0	2
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Bladder spasm
subjects affected / exposed	0 / 3 (0.00%)	2 / 20 (10.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	0	0
Dysuria
subjects affected / exposed	1 / 3 (33.33%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	1	0	0	0
Haematuria
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	3	0	5	0
Nocturia
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Proteinuria
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	2	0
Urinary retention
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	1 / 1 (100.00%)
occurrences all number	0	1	0	1	2
Arthritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	1
Back pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Flank pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Muscle spasms
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Myalgia
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	1	0
Infections and infestations
Urinary tract infection pseudomonal
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	3 / 20 (15.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	1 / 1 (100.00%)
occurrences all number	0	3	0	1	1
Sinusitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Pyelonephritis
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Klebsiella urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0
Herpes simplex
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Epididymitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	2
Cystitis
subjects affected / exposed	1 / 3 (33.33%)	0 / 20 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 3 (33.33%)	2 / 20 (10.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	2	0	0	0
Hypercholesterolaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 20 (5.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	2 / 20 (10.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	3	0	0	0
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	7	0
Hyperkalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 20 (0.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	4	0

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Were there any global substantial amendments to the protocol? Yes

04 Sep 2020

The primary purpose of this amendment was to address regulatory comments regarding eligibility criteria, secondary objective and endpoints, withdrawal criteria, and study conduct and additional feedback from investigators to clarify several errors and omissions.

02 Feb 2021

The sponsor evaluated its strategy in bladder cancer and made a decision to remove pemigatinib from this study. As such, this amendment removed the 3 treatment groups that contained pemigatinib (pemigatinib monotherapy, pemigatinib plus retifanlimab, and pemigatinib followed by retifanlimab). The removal of information on fibroblast growth factor receptor was reflected throughout the protocol.

10 May 2021

The primary purpose of this amendment was to address requested comments and changes from the French Health Authority Review.

01 Mar 2022

The primary purpose of this amendment was to add 2 new treatment groups to the Protocol (retifanlimab plus INCAGN02385 as well as retifanlimab plus INCAGN02385 plus INCAGN02390) and to clarify the radiologic tools used for tumor imaging.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
An Open-Label, Randomized, Phase 2, Umbrella Study 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 (Optimus)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in CD8+ lymphocytes within the resected tumor

Primary: Change from Baseline in CD8+ lymphocytes within the resected tumor

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

Secondary: Number of participants with any ≥Grade 3 TEAE

Secondary: Number of participants with any ≥Grade 3 TEAE

Secondary: Pathological complete response rate

Secondary: Pathological complete response rate

Secondary: Major pathological response

Secondary: Major pathological response

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: An Open-Label, Randomized, Phase 2, Umbrella Study 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 (Optimus)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in CD8+ lymphocytes within the resected tumor

Primary: Change from Baseline in CD8+ lymphocytes within the resected tumor

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

Secondary: Number of participants with any ≥Grade 3 TEAE

Secondary: Number of participants with any ≥Grade 3 TEAE

Secondary: Pathological complete response rate

Secondary: Pathological complete response rate

Secondary: Major pathological response

Secondary: Major pathological response

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Open-Label, Randomized, Phase 2, Umbrella Study 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 (Optimus)