A Phase 2b Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer

Conditions

Bladder Cancer, Urothelial Carcinoma, Urothelial Carcinoma Bladder

Keywords

Non-muscle invasive bladder cancer, Low grade non-muscle invasive bladder cancer, Intermediate risk non-muscle invasive bladder cancer, NMIBC, UGN-102, Mitomycin

Brief summary

This Phase 2b, single-arm, multicenter study evaluated the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC).

Detailed description

Eligible patients were treated with 6 once-weekly intravesical instillations of UGN-102. The ablative effect of UGN-102 was evaluated at the 3-month Visit, which occurred 5 weeks ± 1 week after the last weekly instillation (3 months after initiation of study drug). Response was determined based on visual evaluation by cystoscopy (appearance, number, and size of the lesions) and, if there were remaining lesions, by histopathology of the remaining lesions. Complete response (CR) was defined as having no detectable disease (NDD) and was assessed visually during cystoscopy and also by urine cytology. In the event that the investigator was not sure, and there was suspect tissue, a small biopsy was taken from the suspect tissue to confirm CR in addition to cystoscopy and urine cytology. Patients who achieved a CR continued to have monthly telephone contacts to document any adverse events (AEs) and changes in concomitant medications and were assessed at 6, 9, and 12 months after the first instillation of UGN-102 for evidence of disease recurrence. Patients who had a non-complete response (non-CR) discontinued the study and continued with standard of care according to their treating physician. Safety was determined based on a review of AEs, laboratory assessments, and physical examination findings.

Prasad SM, Louie MJ, Burger B, Tsurutis V, Ugwuoke N, Strauss-Ayali D.

2025-10-11

10.1007/s00280-025-04821-5

Treatment of Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer With UGN-102: Outcomes From the 5-Year Long-Term Extension Study of the Single-Arm, Phase 2b Optima II Study.

Shore ND, Chevli KK, Saltzstein D, Ehrlich Y, Raman JD, Friedman B, Sankin A, Scherr D, Huang WC, Louie MJ, Raju S, Burger B, Meads A, Schoenberg M, OPTIMA II Study.

2025-06-25

10.1016/j.clgc.2025.102392

Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer.

Stover AM, Basak R, Mueller D, Lipman R, Teal R, Hilton A, Giannone K, Waheed M, Smith AB.

2022-05-318 citations

10.1097/ju.0000000000002747

MP54-06 LONGITUDINAL HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN ADULTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER RECEIVING A CHEMOABLATIVE GEL AS A PRIMARY TREATMENT (OPTIMA II: PHASE 2B, SINGLE ARM, OPEN-LABEL TRIAL)

Angela B. Smith, Ramsankar Basak, Dana Mueller, Robert R. Lipman, Randall Teal et al. (9 authors)

The Journal of Urology2022-04-07

10.1097/ju.0000000000002633.06

Angela M. Stover, Ramsankar Basak, Dana Mueller, Angela B. Smith

Journal of Clinical Oncology2021-09-211 citations

10.1200/jco.2020.39.28_suppl.270

PD43-02 PRIMARY CHEMOABLATION OF LOW-GRADE INTERMEDIATE-RISK NON-MUSCLE-INVASIVE BLADDER CANCER USING UGN-102, A MITOMYCIN-CONTAINING REVERSE THERMAL GEL (OPTIMA II): A PHASE 2b, OPEN-LABEL, SINGLE-ARM TRIAL

Kent Chevli, Neal D. Shore, Andrew Trainer, Angela B. Smith, Daniel R. Saltzstein et al. (29 authors)

The Journal of Urology2021-08-04

10.1097/ju.0000000000002057.02

UGN-101 (mitomycin gel): a novel treatment for low-grade upper tract urothelial carcinoma.

Kokorovic A, Matin SF.

2020-07-0312 citations

10.1177/1758835920937950

LBA02-03 CAN TURBT BE AVOIDED? PRIMARY CHEMOABLATION WITH A REVERSE THERMAL GEL CONTAINING MITOMYCIN (UGN-102) IN PATIENTS WITH LOW GRADE INTERMEDIATE RISK NON-MUSCLE INVASIVE BLADDER CANCER

William Huang, Kent Chevli, Andrew Trainer, Angela B. Smith, Daniel R. Saltzstein et al. (26 authors)

The Journal of Urology2020-04-012 citations

10.1097/ju.0000000000000958.03

Interventions

DRUGUGN-102

UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid, with subsequent conversion to a semi-solid gel depot following instillation into the bladder. The UGN-102 admixture for intravesical instillations contains 75 mg mitomycin in 56 mL admixture (1.33 mg mitomycin per 1 mL).

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

1. Willing and able to sign an informed consent and comply with the protocol. 2. Has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at screening or within 6 weeks of screening. 3. Is at intermediate risk of recurrence, defined as having 1 or 2 of the following: * Presence of multiple tumors; * Solitary tumor \> 3 cm; * Recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis). 4. Has negative voiding cytology for high grade (HG) disease at or within 6 weeks of enrollment. 5. Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the participant is female or the female partner of a male participant and is of childbearing potential (defined as premenopausal women who have not been sterilized). 6. Has adequate organ and bone marrow function as determined by routine laboratory tests as below: * Leukocytes ≥ 3,000 per μL; * Absolute neutrophil count ≥ 1,500 per μL; * Platelets ≥ 100,000 per μL; * Hemoglobin ≥ 9.0 g/dL; * Total bilirubin ≤ 1.5 x upper limit of normal (ULN); * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; * Alkaline phosphatase ≤ 2.5 × ULN; * Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. 7. Has no evidence of active urinary tract infection (UTI) at Screening and Baseline visits. * In the case of symptomatic UTI, the patient will be treated with a full course of antibiotics, and study drug will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of study drug is left to the discretion of the Principal Investigator (PI).

Exclusion criteria

1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment. 2. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 2 years. 3. History of HG papillary UC in the past 2 years. 4. Known allergy or sensitivity to mitomycin. 5. Clinically significant urethral stricture that would preclude passage of a urethral catheter. 6. History of pelvic radiotherapy. 7. History of: * Neurogenic bladder; * Active urinary retention; * Any other condition that would prohibit normal voiding. 8. Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper tract urothelial carcinoma (UTUC). 9. Has participated in a study with an investigational agent or device within 30 days of enrollment. 10. History of prior treatment with an intravesical chemotherapeutic agent with the exception of a single dose of chemotherapy immediately after any previous transurethral resection of bladder tumors (TURBT). 11. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the investigator, the patient would be unable to comply with the protocol.

Design outcomes

Primary

Measure	Time frame	Description
Complete Response (CR) Rate for UGN-102 Treatment	3 months after the first 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.

Secondary

Measure	Time frame	Description
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values	Up to 12 months	The number of patients who met PCS criteria for chemistry or hematology parameters post-baseline will be summarized
Number of Participants With Post-baseline PCS Vital Signs Values	Up to 12 months	The number of patients who met PCS criteria for vital signs parameters post-baseline will be summarized
Number of Participants With Post-baseline Clinically Significant (CS) Physical Examination Findings	Up to 12 months	The number of patients with abnormal, CS physical examination findings post-baseline will be summarized
Number of Participants With Post-baseline CS Urology-oriented Physical Examination Findings	Up to 12 months	The number of patients with abnormal, CS urology-oriented physical examination findings post-baseline will be summarized
Durable Complete Response (DCR) Rate	6, 9, and 12 months after the first instillation of UGN-102	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.
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.	Up to 12 months	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).

Other

Measure	Time frame	Description
Mitomycin Maximum Plasma Concentration (Cmax)	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102	Mitomycin Cmax was assessed in a subset of 6 patients treated with UGN-102
Mitomycin Plasma Concentrations	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102	Mitomycin plasma concentrations were assessed in a subset of 6 patients treated with UGN-102
Mitomycin Area Under the Plasma Concentration-time Curve (AUC)	0 (pre-instillation) to 6 hours after the first instillation of UGN-102	Mitomycin AUC was assessed in a subset of 6 patients treated with UGN-102

Countries

Israel, United States

Participant flow

Participants by arm

Arm	Count
UGN-102 6 once-weekly intravesical instillations of UGN-102.	63
Total	63

Withdrawals & dropouts

Period	Reason	FG000
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

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

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 63
other Total, other adverse events	57 / 63
serious Total, serious adverse events	5 / 63

Outcome results

Primary

Complete Response (CR) Rate for UGN-102 Treatment

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.

Time frame: 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)

Arm	Measure	Value (NUMBER)
UGN-102	Complete Response (CR) Rate for UGN-102 Treatment	65.1 percentage of patients

Secondary

Durable Complete Response (DCR) Rate

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.

Time frame: 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)

Arm	Measure	Group	Value (NUMBER)
UGN-102	Durable Complete Response (DCR) Rate	6 months (3 months after CR at the 3-month Visit)	95.1 percentage of patients
UGN-102	Durable Complete Response (DCR) Rate	9 months (6 months after CR at the 3-month Visit)	73.2 percentage of patients
UGN-102	Durable Complete Response (DCR) Rate	12 months (9 months after CR at the 3-month Visit)	61.0 percentage of patients

Secondary

Number of Participants With Post-baseline Clinically Significant (CS) Physical Examination Findings

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

Time frame: Up to 12 months