Bladder Cancer, Urothelial Carcinoma, Urothelial Carcinoma Bladder
Conditions
Keywords
Non-muscle invasive bladder cancer, Low grade non-muscle invasive bladder cancer, Intermediate risk non-muscle invasive bladder cancer, NMIBC, UGN-102, Mitomycin, Transurethral resection of bladder tumors, TURBT
Brief summary
This global, randomized, controlled, open-label Phase 3 study was designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution with or without (±) transurethral resection of bladder tumors (TURBT) versus TURBT alone for the treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).
Detailed description
Eligible patients were randomized in a 1:1 ratio to UGN-102 ± TURBT or TURBT alone. Randomization was stratified by the presence of a previous LG-NMIBC episode within 1 year of the current diagnosis (yes or no). Starting on Day 1, patients randomized to the UGN-102 ± TURBT arm will receive 6 weekly intravesical instillations of UGN-102 and patients randomized to the TURBT alone arm underwent TURBT. All patients returned to the clinic approximately 3 months after the start of treatment for a disease assessment visit. Response to treatment was determined based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions, and voiding urine cytology. Patients confirmed to have a complete response (CR), defined as having no detectable disease (NDD) in the bladder, received no further treatment and entered the Follow-up Period of the study. Patients confirmed to have a non-complete response (NCR) due to residual LG disease in either treatment arm underwent TURBT of any remaining lesions and then entered the Follow-up Period of the study. During the Follow-up Period, patients returned to the clinic every 3 months to determine if they remained disease free. Patients remained on study until completion of all follow-up visits or until disease recurrence, disease progression, or death was documented, whichever occurred first. Patients determined to have a protocol-defined recurrence or progression at any follow-up or unscheduled visit were considered to have completed the study and released to the care of their treating physician. Study enrollment was stopped early by the sponsor to pursue an alternative development strategy for UGN-102 in the treatment of bladder cancer. Patients who had consented at the time the trial terminated were permitted to continue, but follow-up was terminated once the last patient had been followed for 15 months after the start of treatment.
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 under chilled conditions, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.
PROCEDURETURBT
The current standard of care for treatment of LG-IR-NMIBC is TURBT under general anesthesia.
Sponsors
UroGen Pharma Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. 2. Patient who has newly diagnosed or historic LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks of Screening. 3. Has intermediate risk disease, 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. Negative voiding cytology for HG disease within 6 weeks of Screening. 5. Has adequate organ and bone marrow function as determined by the following routine laboratory tests: * Leukocytes ≥ 3,000 cells per μL; * Absolute neutrophil count ≥ 1,500 cells 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 (ALP) ≤ 2.5 × ULN; * Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. 6. Has no evidence of active urinary tract infection (UTI). 7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants. Women of childbearing potential (defined as premenopausal women who have not been sterilized), including female patients and female partners of male patients, must be willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post-treatment.
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 1 year. 3. History of HG papillary UC in the past 2 years. 4. Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be readily managed. 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 UC. 9. Current tumor stage of T1. 10. 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. 11. History of prior treatment with an intravesical chemotherapeutic agent except for a single dose of chemotherapy immediately after any previous TURBT. 12. Has previously participated in a study in which they received UGN-102. 13. Has participated in a study with an investigational agent or device within 30 days of randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | 15 months | DFS is defined as the time from randomization until the earliest date of any of the following events: failure to be rendered free of local disease at the 3-month Visit (TURBT arm only), recurrence of LG disease after the 3-month Visit (ie, during the Follow-up Period), progression to high-grade (HG) disease, or death due to any cause. Summarized is the Kaplan-Meier estimated probability of remaining event-free at 15 months from randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | 3 months | CRR is defined as the percentage of patients who achieve CR at the 3-month Visit. |
| Duration of Response (DOR) | 12 months | DOR is defined as the time from first documented CR until the earliest date of recurrence of LG disease, progression to HG disease, or death due to any cause. DOR applies only to patients who achieve CR at the 3-month Visit. Summarized is the Kaplan-Meier estimated probability of remaining in response at 12 months after 3-month CR. |
| Observed CRR at Scheduled Disease Assessment Time Points | 12 months | Observed CRR at scheduled disease assessment time points is defined as the percentage of patients who achieve CR at the 3-month Visit and maintain CR up to a particular follow-up visit. Summarized is the observed percentage of patients remaining in response at 3, 6, 9, and 12 months after 3-month CR. |
| Number of TURBTs | 3 months | Number of TURBTs is defined as the average number of per protocol TURBTs per patient in each arm. Per protocol TURBTs are defined as the Day 1 TURBT for patients in the TURBT alone arm and TURBT due to residual LG disease at the 3-month disease assessment in either arm. |
| Time to Recurrence (TTR) | 15 months | TTR is defined as the time from randomization until the earliest date of any of the following events: failure to be rendered free of local disease at the 3-month Visit (TURBT arm only), recurrence of LG disease after the 3-month Visit (ie, during the Follow-up Period), or progression to HG disease. Summarized is the Kaplan-Meier estimated probability of remaining event-free at 15 months from randomization. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Up to 21 months | The number of patients with each type of event will be summarized. TEAEs were defined as adverse events (AEs) that occurred on or after the day of first instillation of UGN-102 for patients in the UGN-102 ± TURBT arm or the day of initial TURBT for patients in the TURBT alone arm, or pre-treatment events that worsened during the study. |
| Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Up to 6 months | The number of patients with each type of event will be summarized. |
| Number of Participants With Post-baseline PCS Serum Chemistry Values | Up to 6 months | The number of patients with each type of event will be summarized. |
| Changes From Baseline in Health-related Quality of Life | Pre-treatment to 3 months after the start of treatment | The European Organisation for Research and Treatment of Cancer (EORTC) 24-item quality of life questionnaire for patients with NMIBC (QLQ-NMIBC24) is a patient-reported instrument that assesses 11 domains (urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, sexual intimacy, risk of contaminating partner, male sexual problems, female sexual problems, sexual function, and sexual enjoyment). All of the domains range in score from 0 to 100 with lower scores reflecting better functioning/quality of life and higher scores reflecting worse functioning/quality of life. Summarized is the change from baseline in domain scores at the 3-month Visit. Changes in domain scores were calculated for patients with non-missing answers at both time points. |
Countries
Bulgaria, Estonia, Georgia, Israel, Latvia, Poland, Russia, Serbia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UGN-102 ± TURBT 6 weekly intravesical instillations of UGN-102 (75 mg mitomycin) starting on Day 1 + TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the start of treatment with UGN-102). | 142 |
| TURBT Alone TURBT on Day 1 + repeat TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the initial TURBT). | 140 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Disease Progression | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Noncompliance | 0 | 1 |
| Overall Study | Not Eligible | 1 | 3 |
| Overall Study | Other Reason | 1 | 2 |
| Overall Study | Physician Decision | 3 | 5 |
| Overall Study | Randomization Error | 3 | 0 |
| Overall Study | Sponsor Requirement | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 16 |
Baseline characteristics
| Characteristic | Total | TURBT Alone | UGN-102 ± TURBT |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 168 Participants | 77 Participants | 91 Participants |
| Age, Categorical Between 18 and 65 years | 114 Participants | 63 Participants | 51 Participants |
| Age, Continuous | 68 years | 67 years | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 277 Participants | 137 Participants | 140 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Previous LG-NMIBC Episode(s) No | 163 Participants | 75 Participants | 88 Participants |
| Previous LG-NMIBC Episode(s) Yes | 119 Participants | 65 Participants | 54 Participants |
| Previous LG-NMIBC Episode(s) Within 1 Year No | 201 Participants | 100 Participants | 101 Participants |
| Previous LG-NMIBC Episode(s) Within 1 Year Yes | 81 Participants | 40 Participants | 41 Participants |
| Prior TURBT(s) No | 166 Participants | 76 Participants | 90 Participants |
| Prior TURBT(s) Yes | 116 Participants | 64 Participants | 52 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 279 Participants | 139 Participants | 140 Participants |
| Region of Enrollment Bulgaria | 63 participants | 26 participants | 37 participants |
| Region of Enrollment Estonia | 18 participants | 8 participants | 10 participants |
| Region of Enrollment Georgia | 30 participants | 15 participants | 15 participants |
| Region of Enrollment Israel | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Latvia | 16 participants | 7 participants | 9 participants |
| Region of Enrollment Poland | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Russia | 91 participants | 47 participants | 44 participants |
| Region of Enrollment Serbia | 5 participants | 4 participants | 1 participants |
| Region of Enrollment Ukraine | 31 participants | 20 participants | 11 participants |
| Region of Enrollment United States | 25 participants | 11 participants | 14 participants |
| Sex: Female, Male Female | 84 Participants | 47 Participants | 37 Participants |
| Sex: Female, Male Male | 198 Participants | 93 Participants | 105 Participants |
| Smoking History Non-smoker | 136 Participants | 73 Participants | 63 Participants |
| Smoking History Smoker | 146 Participants | 67 Participants | 79 Participants |
| Tumor Count Missing | 12 Participants | 6 Participants | 6 Participants |
| Tumor Count Multiple | 176 Participants | 94 Participants | 82 Participants |
| Tumor Count Single | 94 Participants | 40 Participants | 54 Participants |
| Tumor Size ≤ 3 cm | 142 Participants | 73 Participants | 69 Participants |
| Tumor Size > 3 cm | 126 Participants | 59 Participants | 67 Participants |
| Tumor Size Missing | 14 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 138 | 1 / 132 |
| other Total, other adverse events | 102 / 138 | 62 / 132 |
| serious Total, serious adverse events | 12 / 138 | 7 / 132 |
Outcome results
Primary
Disease-free Survival (DFS)
DFS is defined as the time from randomization until the earliest date of any of the following events: failure to be rendered free of local disease at the 3-month Visit (TURBT arm only), recurrence of LG disease after the 3-month Visit (ie, during the Follow-up Period), progression to high-grade (HG) disease, or death due to any cause. Summarized is the Kaplan-Meier estimated probability of remaining event-free at 15 months from randomization.
Time frame: 15 months
Population: All randomized patients regardless of whether the treatment was administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UGN-102 ± TURBT | Disease-free Survival (DFS) | 72.0 percentage of participants |
| TURBT Alone | Disease-free Survival (DFS) | 49.5 percentage of participants |
95% CI: [0.29, 0.68]
Secondary
Changes From Baseline in Health-related Quality of Life
The European Organisation for Research and Treatment of Cancer (EORTC) 24-item quality of life questionnaire for patients with NMIBC (QLQ-NMIBC24) is a patient-reported instrument that assesses 11 domains (urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, sexual intimacy, risk of contaminating partner, male sexual problems, female sexual problems, sexual function, and sexual enjoyment). All of the domains range in score from 0 to 100 with lower scores reflecting better functioning/quality of life and higher scores reflecting worse functioning/quality of life. Summarized is the change from baseline in domain scores at the 3-month Visit. Changes in domain scores were calculated for patients with non-missing answers at both time points.
Time frame: Pre-treatment to 3 months after the start of treatment
Population: All patients who received any dose of UGN-102 (treatment arm) or at least one TURBT intervention (control arm). At the time of the 3-month Visit, patients had received only the primary intervention (6 weekly intravesical instillations of UGN-102 starting on Day 1 or TURBT on Day 1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Future Worries | -12.7 score on a scale | Standard Deviation 26.49 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Sexual Intimacy | 0.0 score on a scale | Standard Deviation 19.86 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Intravesical Treatment Issues | -4.0 score on a scale | Standard Deviation 25.61 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Risk of Contaminating Partner | 1.6 score on a scale | Standard Deviation 26.12 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Bloating and Flatulence | -7.7 score on a scale | Standard Deviation 18.03 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Female Sexual Problems | -10.0 score on a scale | Standard Deviation 16.1 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Malaise | -4.4 score on a scale | Standard Deviation 13.58 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Sexual Function | 0.4 score on a scale | Standard Deviation 18.02 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Male Sexual Problems | 0.9 score on a scale | Standard Deviation 32.99 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Sexual Enjoyment | 8.7 score on a scale | Standard Deviation 36.97 |
| UGN-102 ± TURBT | Changes From Baseline in Health-related Quality of Life | Urinary Symptoms | -10.7 score on a scale | Standard Deviation 17.88 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Sexual Enjoyment | -1.0 score on a scale | Standard Deviation 32.26 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Urinary Symptoms | -4.5 score on a scale | Standard Deviation 20.04 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Malaise | -1.1 score on a scale | Standard Deviation 16.41 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Intravesical Treatment Issues | -2.9 score on a scale | Standard Deviation 25.09 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Future Worries | -8.3 score on a scale | Standard Deviation 26.74 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Bloating and Flatulence | -3.0 score on a scale | Standard Deviation 16.68 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Male Sexual Problems | -0.6 score on a scale | Standard Deviation 30.75 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Sexual Intimacy | 3.6 score on a scale | Standard Deviation 30.12 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Risk of Contaminating Partner | 0.0 score on a scale | Standard Deviation 16.8 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Female Sexual Problems | -8.9 score on a scale | Standard Deviation 15.26 |
| TURBT Alone | Changes From Baseline in Health-related Quality of Life | Sexual Function | -1.6 score on a scale | Standard Deviation 22.2 |
Secondary
Complete Response Rate (CRR)
CRR is defined as the percentage of patients who achieve CR at the 3-month Visit.
Time frame: 3 months
Population: All randomized patients regardless of whether the treatment was administered. At the time of the 3-month Visit, patients had received only the primary intervention (6 weekly intravesical instillations of UGN-102 starting on Day 1 or TURBT on Day 1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UGN-102 ± TURBT | Complete Response Rate (CRR) | 64.8 percentage of participants |
| TURBT Alone | Complete Response Rate (CRR) | 63.6 percentage of participants |
Secondary
Duration of Response (DOR)
DOR is defined as the time from first documented CR until the earliest date of recurrence of LG disease, progression to HG disease, or death due to any cause. DOR applies only to patients who achieve CR at the 3-month Visit. Summarized is the Kaplan-Meier estimated probability of remaining in response at 12 months after 3-month CR.
Time frame: 12 months
Population: All patients who achieved CR at the 3-month disease assessment. Patients who achieved CR at 3 months received only the primary intervention (6 weekly intravesical instillations of UGN-102 starting on Day 1 or TURBT on Day 1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UGN-102 ± TURBT | Duration of Response (DOR) | 79.7 percentage of participants |
| TURBT Alone | Duration of Response (DOR) | 67.7 percentage of participants |
95% CI: [0.24, 0.86]
Secondary
Number of Participants With Post-baseline PCS Serum Chemistry Values
The number of patients with each type of event will be summarized.
Time frame: Up to 6 months
Population: All patients who received any dose of UGN-102 (treatment arm) or at least one TURBT intervention (control arm) and who had non-missing laboratory values at the specified time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Aspartate aminotransferase > 3 × ULN | 2 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Potassium < 3.0 mEq/L | 0 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Creatinine > 2.2 mg/dL | 0 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Potassium > 5.5 mEq/L | 18 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Bilirubin > 1.5 × ULN | 3 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Sodium ≤ 130 mEq/L | 2 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Gamma glutamyl transferase > 2.5 × ULN | 5 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Sodium > 150 mEq/L | 2 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline PCS Serum Chemistry Values | Alanine aminotransferase > 3 × upper limit of normal (ULN) | 2 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Sodium > 150 mEq/L | 0 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Alanine aminotransferase > 3 × upper limit of normal (ULN) | 1 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Aspartate aminotransferase > 3 × ULN | 1 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Bilirubin > 1.5 × ULN | 2 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Creatinine > 2.2 mg/dL | 1 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Gamma glutamyl transferase > 2.5 × ULN | 1 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Potassium < 3.0 mEq/L | 1 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Potassium > 5.5 mEq/L | 10 Participants |
| TURBT Alone | Number of Participants With Post-baseline PCS Serum Chemistry Values | Sodium ≤ 130 mEq/L | 1 Participants |
Secondary
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values
The number of patients with each type of event will be summarized.
Time frame: Up to 6 months
Population: All patients who received any dose of UGN-102 (treatment arm) or at least one TURBT intervention (control arm) and who had non-missing laboratory values at the specified time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 ± TURBT | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Hemoglobin < 0.8 × lower limit of normal and > 20% decrease from baseline | 4 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Leukocytes ≤ 2.8 × 10^3/μL | 4 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Leukocytes ≥ 16.0 × 10^3/μL | 1 Participants |
| UGN-102 ± TURBT | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Platelets < 75 × 10^3/μL | 1 Participants |
| TURBT Alone | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Platelets < 75 × 10^3/μL | 0 Participants |
| TURBT Alone | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Hemoglobin < 0.8 × lower limit of normal and > 20% decrease from baseline | 1 Participants |
| TURBT Alone | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Leukocytes ≥ 16.0 × 10^3/μL | 0 Participants |
| TURBT Alone | Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values | Leukocytes ≤ 2.8 × 10^3/μL | 1 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest
The number of patients with each type of event will be summarized. TEAEs were defined as adverse events (AEs) that occurred on or after the day of first instillation of UGN-102 for patients in the UGN-102 ± TURBT arm or the day of initial TURBT for patients in the TURBT alone arm, or pre-treatment events that worsened during the study.
Time frame: Up to 21 months
Population: All patients who received any dose of UGN-102 (treatment arm) or at least one TURBT intervention (control arm).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGN-102 ± TURBT | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any TEAEs | 104 Participants |
| UGN-102 ± TURBT | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any serious TEAEs | 12 Participants |
| UGN-102 ± TURBT | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any TEAEs of special interest | 78 Participants |
| TURBT Alone | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any TEAEs | 63 Participants |
| TURBT Alone | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any serious TEAEs | 7 Participants |
| TURBT Alone | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest | Any TEAEs of special interest | 36 Participants |
Secondary
Number of TURBTs
Number of TURBTs is defined as the average number of per protocol TURBTs per patient in each arm. Per protocol TURBTs are defined as the Day 1 TURBT for patients in the TURBT alone arm and TURBT due to residual LG disease at the 3-month disease assessment in either arm.
Time frame: 3 months
Population: All patients who received any dose of UGN-102 (treatment arm) or at least one TURBT intervention (control arm).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| UGN-102 ± TURBT | Number of TURBTs | 0.2 TURBT procedures | Standard Deviation 0.38 |
| TURBT Alone | Number of TURBTs | 1.1 TURBT procedures | Standard Deviation 0.34 |
Secondary
Observed CRR at Scheduled Disease Assessment Time Points
Observed CRR at scheduled disease assessment time points is defined as the percentage of patients who achieve CR at the 3-month Visit and maintain CR up to a particular follow-up visit. Summarized is the observed percentage of patients remaining in response at 3, 6, 9, and 12 months after 3-month CR.
Time frame: 12 months
Population: All patients who achieved CR at the 3-month disease assessment. Patients who achieved CR at 3 months received only the primary intervention (6 weekly intravesical instillations of UGN-102 starting on Day 1 or TURBT on Day 1).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UGN-102 ± TURBT | Observed CRR at Scheduled Disease Assessment Time Points | 6 Months After 3-Month CR | 80.4 percentage of participants |
| UGN-102 ± TURBT | Observed CRR at Scheduled Disease Assessment Time Points | 3 Months After 3-Month CR | 92.4 percentage of participants |
| UGN-102 ± TURBT | Observed CRR at Scheduled Disease Assessment Time Points | 9 Months After 3-Month CR | 75.0 percentage of participants |
| UGN-102 ± TURBT | Observed CRR at Scheduled Disease Assessment Time Points | 12 Months After 3-Month CR | 71.7 percentage of participants |
| TURBT Alone | Observed CRR at Scheduled Disease Assessment Time Points | 12 Months After 3-Month CR | 55.1 percentage of participants |
| TURBT Alone | Observed CRR at Scheduled Disease Assessment Time Points | 9 Months After 3-Month CR | 57.3 percentage of participants |
| TURBT Alone | Observed CRR at Scheduled Disease Assessment Time Points | 3 Months After 3-Month CR | 71.9 percentage of participants |
| TURBT Alone | Observed CRR at Scheduled Disease Assessment Time Points | 6 Months After 3-Month CR | 62.9 percentage of participants |
Secondary
Time to Recurrence (TTR)
TTR is defined as the time from randomization until the earliest date of any of the following events: failure to be rendered free of local disease at the 3-month Visit (TURBT arm only), recurrence of LG disease after the 3-month Visit (ie, during the Follow-up Period), or progression to HG disease. Summarized is the Kaplan-Meier estimated probability of remaining event-free at 15 months from randomization.
Time frame: 15 months
Population: All randomized patients regardless of whether the treatment was administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UGN-102 ± TURBT | Time to Recurrence (TTR) | 72.0 percentage of participants |
| TURBT Alone | Time to Recurrence (TTR) | 50.3 percentage of participants |
95% CI: [0.3, 0.7]