Trial Outcomes & Findings for A Phase 2b Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer (NCT NCT03558503)

NCT ID: NCT03558503

Last Updated: 2022-09-16

Results Overview

To evaluate the tumor ablative effect of UGN-102 in patients with LG NMIBC. CR rate was defined as the percentage of patients with no detectable disease (NDD) as determined by cystoscopy, for cause biopsy, and urine cytology.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: 3 months after the first instillation of UGN-102
• Results posted on: 2022-09-16

Participant Flow

Participant milestones

Measure	UGN-102 6 once-weekly intravesical instillations of UGN-102.
Overall Study STARTED	63
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	UGN-102 6 once-weekly intravesical instillations of UGN-102.
Overall Study Adverse Event	1
Overall Study Death	1
Overall Study Refused to come in for the final 12-month assessment due to COVID-19	1

Baseline Characteristics

Data on tumor size were missing for 2 patients.

Baseline characteristics by cohort

Measure	UGN-102 n=63 Participants 6 once-weekly intravesical instillations of UGN-102.
Age, Categorical <=18 years	0 Participants n=63 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=63 Participants
Age, Categorical >=65 years	36 Participants n=63 Participants
Age, Continuous	68 years n=63 Participants
Sex: Female, Male Female	25 Participants n=63 Participants
Sex: Female, Male Male	38 Participants n=63 Participants
Race/Ethnicity, Customized Caucasian	55 Participants n=63 Participants
Race/Ethnicity, Customized African American	1 Participants n=63 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=63 Participants
Race/Ethnicity, Customized Asian	3 Participants n=63 Participants
Race/Ethnicity, Customized Other	1 Participants n=63 Participants
Tumor Size <=3 centimeters	44 Participants n=61 Participants • Data on tumor size were missing for 2 patients.
Tumor Size >3 centimeters	17 Participants n=61 Participants • Data on tumor size were missing for 2 patients.
Tumor Number Single	11 Participants n=61 Participants • Data on tumor number were missing for 2 patients.
Tumor Number Multiple	50 Participants n=61 Participants • Data on tumor number were missing for 2 patients.
Visual Appearance of Lesions Papillary	63 participants n=63 Participants
Visual Appearance of Lesions Flat	2 participants n=63 Participants
Visual Appearance of Lesions Other	2 participants n=63 Participants
Tumor Staging Noninvasive papillary carcinoma	62 participants n=63 Participants
Tumor Staging Other	2 participants n=63 Participants
Tumor Grading Papillary urothelial carcinoma, low grade	62 participants n=63 Participants
Tumor Grading Papillary urothelial neoplasm of low malignant potential	1 participants n=63 Participants
Tumor Grading Other	2 participants n=63 Participants
Any Previous Low Grade Non-muscle-invasive Bladder Cancer (LG NMIBC) Episode Yes	49 Participants n=63 Participants
Any Previous Low Grade Non-muscle-invasive Bladder Cancer (LG NMIBC) Episode No	14 Participants n=63 Participants
Previous LG NMIBC Episode Within 1 Year of Current Diagnosis Yes	28 Participants n=63 Participants
Previous LG NMIBC Episode Within 1 Year of Current Diagnosis No	35 Participants n=63 Participants
Number of Previous LG NMIBC Episodes 0	14 Participants n=63 Participants
Number of Previous LG NMIBC Episodes 1-2	17 Participants n=63 Participants
Number of Previous LG NMIBC Episodes >2	32 Participants n=63 Participants
Number of Prior Transurethral Resection of Bladder Tumors (TURBT)	4 TURBTs n=49 Participants • Data on prior TURBT were summarized for patients with a previous LG NMIBC episode.
Patients With Number of Prior TURBT 0	2 Participants n=49 Participants • Data on prior TURBT were summarized for patients with a previous LG NMIBC episode.
Patients With Number of Prior TURBT 1	10 Participants n=49 Participants • Data on prior TURBT were summarized for patients with a previous LG NMIBC episode.
Patients With Number of Prior TURBT 2	9 Participants n=49 Participants • Data on prior TURBT were summarized for patients with a previous LG NMIBC episode.
Patients With Number of Prior TURBT >=3	28 Participants n=49 Participants • Data on prior TURBT were summarized for patients with a previous LG NMIBC episode.
Days Since Last TURBT at Time of Day 1 <=365	23 Participants n=47 Participants • Days since last TURBT were summarized for patients with a previous LG NMIBC episode and a prior TURBT.
Days Since Last TURBT at Time of Day 1 >365	24 Participants n=47 Participants • Days since last TURBT were summarized for patients with a previous LG NMIBC episode and a prior TURBT.

PRIMARY outcome

Timeframe: 3 months after the first instillation of UGN-102

Population: Intent-to-treat (ITT) analysis set (all patients who were enrolled into the study and received at least one instillation of UGN-102)

To evaluate the tumor ablative effect of UGN-102 in patients with LG NMIBC. CR rate was defined as the percentage of patients with no detectable disease (NDD) as determined by cystoscopy, for cause biopsy, and urine cytology.

Outcome measures

Measure	UGN-102 n=63 Participants 6 once-weekly intravesical instillations of UGN-102.
Complete Response (CR) Rate for UGN-102 Treatment	65.1 percentage of patients Interval 52.0 to 76.7

SECONDARY outcome

Timeframe: 6, 9, and 12 months after the first instillation of UGN-102

Population: 3-month CR analysis set (patients who achieved CR at the 3-month Visit)

To evaluate the durability of response in patients with LG NMIBC who achieve CR. DCR rate was defined as the percentage of patients who maintained CR at the respective time point.

Outcome measures

Measure	UGN-102 n=41 Participants 6 once-weekly intravesical instillations of UGN-102.
Durable Complete Response (DCR) Rate 6 months (3 months after CR at the 3-month Visit)	95.1 percentage of patients Interval 83.5 to 99.4
Durable Complete Response (DCR) Rate 9 months (6 months after CR at the 3-month Visit)	73.2 percentage of patients Interval 57.1 to 85.8
Durable Complete Response (DCR) Rate 12 months (9 months after CR at the 3-month Visit)	61.0 percentage of patients Interval 44.5 to 75.8

SECONDARY outcome

Timeframe: Up to 12 months

Population: ITT analysis set (all patients who were enrolled into the study and received at least one instillation of UGN-102), which is identical to the safety analysis set for this study

The number of patients with each type of event will be summarized. Adverse event severity was graded according to Common Terminology Criteria for Adverse Events version 5.0 as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), Grade 5 (fatal).

Outcome measures

Measure	UGN-102 n=63 Participants 6 once-weekly intravesical instillations of UGN-102.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Any TEAEs	57 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Any study drug or procedure related TEAEs	40 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Maximum severity Grade 1	26 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Maximum severity Grade 2	24 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Maximum severity Grade 3	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Maximum severity Grade 4	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Maximum severity Grade 5	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Any TEAEs leading to treatment discontinuation	6 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs. Any serious TEAEs	5 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: ITT analysis set (all patients who were enrolled into the study and received at least one instillation of UGN-102), which is identical to the safety analysis set for this study

The number of patients who met PCS criteria for chemistry or hematology parameters post-baseline will be summarized

Outcome measures

Measure	UGN-102 n=63 Participants 6 once-weekly intravesical instillations of UGN-102.
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values Any PCS chemistry value	8 Participants
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values Any PCS hematology value	4 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: ITT analysis set (all patients who were enrolled into the study and received at least one instillation of UGN-102), which is identical to the safety analysis set for this study

The number of patients who met PCS criteria for vital signs parameters post-baseline will be summarized

Outcome measures

Measure	UGN-102 n=63 Participants 6 once-weekly intravesical instillations of UGN-102.
Number of Participants With Post-baseline PCS Vital Signs Values	8 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: ITT analysis set (all patients who were enrolled into the study and received at least one instillation of UGN-102), which is identical to the safety analysis set for this study

The number of patients with abnormal, CS physical examination findings post-baseline will be summarized

Outcome measures

Measure	UGN-102 n=63 Participants 6 once-weekly intravesical instillations of UGN-102.
Number of Participants With Post-baseline Clinically Significant (CS) Physical Examination Findings	0 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: ITT analysis set (all patients who were enrolled into the study and received at least one instillation of UGN-102), which is identical to the safety analysis set for this study

The number of patients with abnormal, CS urology-oriented physical examination findings post-baseline will be summarized

Outcome measures

Measure	UGN-102 n=63 Participants 6 once-weekly intravesical instillations of UGN-102.
Number of Participants With Post-baseline CS Urology-oriented Physical Examination Findings	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102

Population: Pharmacokinetic (PK) analysis set (all patients who consented to provide blood samples for PK analysis and had at least 1 plasma sample for evaluation of PK properties of mitomycin following an initial instillation of UGN-102)

Mitomycin plasma concentrations were assessed in a subset of 6 patients treated with UGN-102

Outcome measures

Measure	UGN-102 n=6 Participants 6 once-weekly intravesical instillations of UGN-102.
Mitomycin Plasma Concentrations 1 hour post-instillation	0.60 ng/mL Standard Deviation 0.42
Mitomycin Plasma Concentrations Pre-instillation	0 ng/mL Standard Deviation 0
Mitomycin Plasma Concentrations 0.5 hours post-instillation	0.75 ng/mL Standard Deviation 0.57
Mitomycin Plasma Concentrations 2 hours post-instillation	0.34 ng/mL Standard Deviation 0.17
Mitomycin Plasma Concentrations 3 hours post-instillation	1.88 ng/mL Standard Deviation 3.13
Mitomycin Plasma Concentrations 4 hours post-instillation	1.93 ng/mL Standard Deviation 3.49
Mitomycin Plasma Concentrations 5 hours post-instillation	0.57 ng/mL Standard Deviation 0.61
Mitomycin Plasma Concentrations 6 hours post-instillation	0.32 ng/mL Standard Deviation 0.32

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 (pre-instillation) to 6 hours after the first instillation of UGN-102

Population: PK analysis set (all patients who consented to provide blood samples for PK analysis and had at least 1 plasma sample for evaluation of PK properties of mitomycin following an initial instillation of UGN-102)

Mitomycin AUC was assessed in a subset of 6 patients treated with UGN-102

Outcome measures

Measure	UGN-102 n=6 Participants 6 once-weekly intravesical instillations of UGN-102.
Mitomycin Area Under the Plasma Concentration-time Curve (AUC)	5.69 ng*h/mL Standard Deviation 7.30

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102

Population: PK analysis set (all patients who consented to provide blood samples for PK analysis and had at least 1 plasma sample for evaluation of PK properties of mitomycin following an initial instillation of UGN-102)

Mitomycin Cmax was assessed in a subset of 6 patients treated with UGN-102

Outcome measures

Measure	UGN-102 n=6 Participants 6 once-weekly intravesical instillations of UGN-102.
Mitomycin Maximum Plasma Concentration (Cmax)	2.27 ng/mL Standard Deviation 3.33

Adverse Events

UGN-102

Serious events: 5 serious events

Other events: 57 other events

Deaths: 1 deaths

Serious adverse events

Measure	UGN-102 n=63 participants at risk 6 once-weekly intravesical instillations of UGN-102.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukemia	1.6% 1/63 • Up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastroenteropancreatic neuroendocrine tumor disease	1.6% 1/63 • Up to 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma metastatic	1.6% 1/63 • Up to 12 months
Cardiac disorders Cardiac disorder	1.6% 1/63 • Up to 12 months
Cardiac disorders Stress cardiomyopathy	1.6% 1/63 • Up to 12 months
Infections and infestations Pneumonia	1.6% 1/63 • Up to 12 months
Infections and infestations Pneumonia klebsiella	1.6% 1/63 • Up to 12 months
Renal and urinary disorders Hematuria	1.6% 1/63 • Up to 12 months
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.6% 1/63 • Up to 12 months

Other adverse events

Measure	UGN-102 n=63 participants at risk 6 once-weekly intravesical instillations of UGN-102.
Renal and urinary disorders Dysuria	41.3% 26/63 • Up to 12 months
Renal and urinary disorders Pollakiuria	20.6% 13/63 • Up to 12 months
Renal and urinary disorders Hematuria	14.3% 9/63 • Up to 12 months
Renal and urinary disorders Micturition urgency	14.3% 9/63 • Up to 12 months
Renal and urinary disorders Urinary tract infection	14.3% 9/63 • Up to 12 months
Renal and urinary disorders Urinary incontinence	7.9% 5/63 • Up to 12 months
Renal and urinary disorders Nocturia	6.3% 4/63 • Up to 12 months
Renal and urinary disorders Urinary retention	6.3% 4/63 • Up to 12 months
Reproductive system and breast disorders Pruritus genital	6.3% 4/63 • Up to 12 months
Reproductive system and breast disorders Vulvovaginal discomfort	6.3% 4/63 • Up to 12 months
General disorders Fatigue	11.1% 7/63 • Up to 12 months
Injury, poisoning and procedural complications Accidental exposure to product	6.3% 4/63 • Up to 12 months

Additional Information

Elyse Seltzer, MD

UroGen Pharma

Phone: 1-646-492-8518

Email: elyse.seltzer@urogen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place