Superficial Bladder Cancer
Conditions
Keywords
IFN, BCG-unresponsive, Non-Muscle Invasive Bladder Cancer (NMIBC)
Brief summary
Previous multi-dose Phase I and Phase II clinical studies have demonstrated that ADSTILADRIN is a safe and effective treatment for BCG-refractory and recurrent NMIBC. This Phase III study is designed to expand those observations using a high dose of ADSTILADRIN in patients that are BCG Unresponsive which refers to patients with high-grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG.
Detailed description
Recombinant IFN alpha2b has pleiotropic effects that contribute to antitumor activity in Non-Muscle Invasive Bladder Cancer (NMIBC). ADSTILADRIN is a non-replicating adenovirus vector harboring the human IFN alpha2b gene. When combined with the excipient Syn3, intravesical administration of the rAd-IFN results in transduction of the virus into the epithelial cell lining in the bladder. The IFN alpha2b gene is incorporated into the cellular DNA resulting in the synthesis and expression of large amounts of IFN alpha2b protein. Clinical studies have confirmed that IFN alpha2b protein can be measured in the urine of patients treated with ADSTILADRIN within 24 hours after dosing.
Interventions
BIOLOGICALADSTILADRIN
Sponsors
FKD Therapies Oy
Society of Urologic Oncology Clinical Trials Consortium
Ferring Pharmaceuticals
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. Aged 18 years or older at the time of consent 2. Able to give informed consent 3. Had, at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only; Ta/T1 high-grade disease with concomitant CIS; or Ta/T1 high-grade disease without concomitant CIS 4. Are BCG Unresponsive which refers to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term BCG unresponsive included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response (CR) to BCG, relapsed with high-grade CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria defined the patients who were eligible for inclusion in the study: * Had received at least 2 previous courses of BCG within a 12 month period. This was defined as at least 5 of 6 induction BCG instillations and at least 2 out of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG was not given; * Exception: those who had T1 high-grade disease at first evaluation after induction BCG alone (at least 5 of 6 doses) qualified in the absence of disease progression. * At the time of tumor recurrence, patients with CIS alone or high-grade Ta/T1 with CIS were within 12 months of last exposure to BCG and patients with high-grade Ta/T1 without CIS were within 6 months of last exposure to BCG; * No maximum limit to the amount of BCG administered; and * All visible papillary tumors were required to be resected and those with persistent T1 disease on transurethral resection of bladder tumor (TURBT) underwent an additional re-TURBT within 14 to 60 days prior to beginning study treatment. Obvious areas of CIS should also be fulgurated. 5. Available for the whole duration of the study 6. Life expectancy \>2 years, in the opinion of the investigator 7. Eastern Cooperative Oncology Group (ECOG) status 2 or less 8. Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or magnetic resonance imaging (MRI) with or without urogram performed within 6 months of enrollment 9. Patients with prostate cancer on active surveillance at low risk for progression, defined as Prostate-Specific Antigen (PSA) \< 10 ng/dL, Gleason score 6 and clinical stage tumor-1 (cT1) were permitted to be in the study at the discretion of the investigator (see exclusion criterion 10). 10. Female patients of childbearing potential were required to use maximally effective birth control during the period of therapy, were required to use contraception for 1 month following the last study drug infusion and were required to have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients were required to be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. 'Maximally effective birth control' meant that the patient, if sexually active, used a combination of two methods of birth control that were approved and recognized to be effective by Regulatory Agencies 11. Male patients were required to be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion; and 12. Adequate lab values
Exclusion criteria
1. Current or previous evidence of muscle invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples of increased risk of metastatic disease included (but were not limited to): * Presence of lymphovascular invasion and/micropapillary disease as shown in the histology of the biopsy sample; and * Patients with T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumor 2. Current systemic therapy for bladder cancer 3. Current or prior pelvic external beam radiotherapy within 5 years of entry 4. Prior treatment with adenovirus-based drugs 5. Suspected hypersensitivity to IFN alfa2b 6. Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily treated, patients could have entered the study) 7. Clinically significant and unexplained elevated liver or renal function tests 8. Women who were pregnant or lactating or refused to commit to use contraception throughout the study 9. Any other significant disease or other clinical findings which, in the opinion of the investigator, prevented study entry 10. History of malignancy of another organ system within the past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ≤ pathological tumor-2 (pT2) upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also patients with genitourinary cancers other than urothelial cancer or prostate cancer that were under active surveillance were excluded (see inclusion criterion 9) 11. Patients who could not hold instillation for 1 hour 12. Patients who could not tolerate intravesical dosing or intravesical surgical manipulation; and 13. Intravesical therapy within 8 weeks prior to beginning study treatment with the exception of: * cytotoxic agents (e.g. Mitomycin C, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure which was permitted between 14 to 60 days prior to beginning study treatment * previous intravesical BCG therapy, which could be given at least 5 weeks before the diagnostic biopsy required for entry into the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With a Complete Response Rate Based on Patients With Carcinoma in Situ (CIS), With or Without Concomitant High-grade Ta or T1 Papillary Disease. | 12 Months | A patient in the CIS cohort was judged to have achieved CR where urine cytology was reported as normal, atypical, degenerative, reactive, inflammatory, or nonspecific AND cystoscopy was reported as normal or with findings that did not include evidence of low-grade or high-grade recurrence. Bladder biopsy, if performed (not mandatory), demonstrated an absence of low-grade or high-grade recurrence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Durability of Complete Response in Patients With CIS (With or Without Concomitant Ta or T1 Papillary Disease) Who Achieve a Complete Response. | Up to 57 months | Durability of complete response (CR) was defined as the time from first observed CR to the documented treatment failure. Patients without treatment failure were censored at the last disease assessment not showing treatment failure, where treatment failure was defined as high-grade disease recurrence, disease progression, or death, whichever occurred earlier. |
| Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | up to 57 months | Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder. Incidence of HGRF survival at Months 3, 6, 9, and 12, and every 3 months up to Month 24, and then at Months 36, 48, and 57. |
| Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Up to 57 months | HGRF survival was defined as the time from the first dose to the first recurrence of high-grade disease (including muscle-invasive disease progression and death due to any cause). Patients without high-grade disease recurrence were censored at the last disease assessment not showing high-grade disease recurrence. |
| Durability of Response During the Long-term Follow-up Period. | Up to 60 Months | Durability will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder if clinically indicated. |
| Overall Survival Rate in All Patients | 60 Months | Overall survival rate was defined as the time from the first dose to death due to any cause. Patients who were still alive were censored at the last date the patient was known to be alive. Overall survival rate is a Kaplan-Meier estimate of the survivor function at each specific time point. The 95% CI is calculated using the Greenwood's formula with a log-log transformation. Percentage is calculated using the number of patients in the column heading as the denominator. |
| Anti-adenoviral Antibody Levels for Correlation to Response Rate | 12 Months | Measurement of anti-adenoviral antibody levels at each dosing period, withdrawal, and at 12 months were done. A patient was considered to have a positive immunogenic response in anti-adenoviral antibodies if a post-baseline titration demonstrated a greater than a 2-fold dilution increase from baseline. The table represent data at any time during the 12 months period, which means that the patients were included in the Yes group if they at any measurement during the trial had a 2-fold dilution increase from baseline. |
| Safety of ADSTILADRIN | 60 Months | The type, incidence, relatedness and severity of treatment emergent adverse events of ADSTILADRIN as assessed by NCI-CTCAE V4.03 were monitored. |
| Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 60 Months | The incidence of cystectomy is described as the proportion of patients undergoing radical cystectomy for any reason after the first dose, within 12 months, 2 years and 5 years. |
Countries
United States
Participant flow
Recruitment details
Patients enrolled in the study who had at entry, confirmed by a pathology report: CIS only or Ta/T1 high- grade disease with concomitant CIS, or Ta/T1 high-grade disease without concomitant CIS and were BCG unresponsive which referred to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG.
Participants by arm
| Arm | Count |
|---|---|
| Carcinoma in Situ Patients with Carcinoma in situ (CIS) with or without concomitant high-grade Ta or T1 papillary disease | 107 |
| Papillary Disease Patients with high-grade Ta or T1 papillary disease (without concomitant CIS) | 50 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 26 |
| Overall Study | Lost to Follow-up | 11 |
| Overall Study | Other: not due to lack of tolerability | 11 |
| Overall Study | Withdrawal by Subject | 5 |
| Overall Study | Withdrawal of Consent | 9 |
Baseline characteristics
| Characteristic | Carcinoma in Situ | Total | Papillary Disease |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 82 Participants | 119 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 38 Participants | 13 Participants |
| Body Mass Index | 29.38 kg/m^2 STANDARD_DEVIATION 5.7 | 29.34 kg/m^2 STANDARD_DEVIATION 5.5 | 29.28 kg/m^2 STANDARD_DEVIATION 5.1 |
| ECOG Status Total ECOG of 0 | 97 Participants | 140 Participants | 43 Participants |
| ECOG Status Total ECOG of 1 | 7 Participants | 13 Participants | 6 Participants |
| ECOG Status Total ECOG of 2 | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants | 148 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 0 Participants |
| Height | 174.7 cm STANDARD_DEVIATION 9.8 | 173.5 cm STANDARD_DEVIATION 10.1 | 170.9 cm STANDARD_DEVIATION 10.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 8 Participants | 2 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 99 Participants | 146 Participants | 47 Participants |
| Region of Enrollment United States | 107 participants | 157 participants | 50 participants |
| Sex: Female, Male Female | 12 Participants | 28 Participants | 16 Participants |
| Sex: Female, Male Male | 95 Participants | 129 Participants | 34 Participants |
| Weight | 90.14 kg STANDARD_DEVIATION 20.9 | 88.78 kg STANDARD_DEVIATION 20.2 | 85.88 kg STANDARD_DEVIATION 18.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 21 / 107 | 5 / 50 | 26 / 157 |
| other Total, other adverse events | 101 / 107 | 45 / 50 | 146 / 157 |
| serious Total, serious adverse events | 10 / 107 | 9 / 50 | 19 / 157 |
Outcome results
Primary
Number of Patients With a Complete Response Rate Based on Patients With Carcinoma in Situ (CIS), With or Without Concomitant High-grade Ta or T1 Papillary Disease.
A patient in the CIS cohort was judged to have achieved CR where urine cytology was reported as normal, atypical, degenerative, reactive, inflammatory, or nonspecific AND cystoscopy was reported as normal or with findings that did not include evidence of low-grade or high-grade recurrence. Bladder biopsy, if performed (not mandatory), demonstrated an absence of low-grade or high-grade recurrence.
Time frame: 12 Months
Population: Subjects analyzed for this endpoint represent subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carcinoma in Situ | Number of Patients With a Complete Response Rate Based on Patients With Carcinoma in Situ (CIS), With or Without Concomitant High-grade Ta or T1 Papillary Disease. | 55 participants |
Secondary
Anti-adenoviral Antibody Levels for Correlation to Response Rate
Measurement of anti-adenoviral antibody levels at each dosing period, withdrawal, and at 12 months were done. A patient was considered to have a positive immunogenic response in anti-adenoviral antibodies if a post-baseline titration demonstrated a greater than a 2-fold dilution increase from baseline. The table represent data at any time during the 12 months period, which means that the patients were included in the Yes group if they at any measurement during the trial had a 2-fold dilution increase from baseline.
Time frame: 12 Months
Population: Patients with Positive Immunogenic Response in Anti-Adenoviral Antibodies at Post-Baseline based on patients who had achieved High-Grade Recurrence Free Survival at 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carcinoma in Situ | Anti-adenoviral Antibody Levels for Correlation to Response Rate | Yes | 63 Participants |
| Carcinoma in Situ | Anti-adenoviral Antibody Levels for Correlation to Response Rate | No | 26 Participants |
| Papillary Disease | Anti-adenoviral Antibody Levels for Correlation to Response Rate | Yes | 34 Participants |
| Papillary Disease | Anti-adenoviral Antibody Levels for Correlation to Response Rate | No | 11 Participants |
| Total | Anti-adenoviral Antibody Levels for Correlation to Response Rate | Yes | 97 Participants |
| Total | Anti-adenoviral Antibody Levels for Correlation to Response Rate | No | 37 Participants |
Secondary
Durability of Complete Response in Patients With CIS (With or Without Concomitant Ta or T1 Papillary Disease) Who Achieve a Complete Response.
Durability of complete response (CR) was defined as the time from first observed CR to the documented treatment failure. Patients without treatment failure were censored at the last disease assessment not showing treatment failure, where treatment failure was defined as high-grade disease recurrence, disease progression, or death, whichever occurred earlier.
Time frame: Up to 57 months
Population: Patients who achieved CR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carcinoma in Situ | Durability of Complete Response in Patients With CIS (With or Without Concomitant Ta or T1 Papillary Disease) Who Achieve a Complete Response. | 9.72 Months |
Secondary
Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS)
HGRF survival was defined as the time from the first dose to the first recurrence of high-grade disease (including muscle-invasive disease progression and death due to any cause). Patients without high-grade disease recurrence were censored at the last disease assessment not showing high-grade disease recurrence.
Time frame: Up to 57 months
Population: Patients with no recurrence of high-grade disease
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Carcinoma in Situ | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | HGRF Survival | 5.95 Months |
| Carcinoma in Situ | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 57 months | 13.2 Months |
| Carcinoma in Situ | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 48 months | 16.7 Months |
| Carcinoma in Situ | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 36 months | 19.3 Months |
| Papillary Disease | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 36 months | 32.7 Months |
| Papillary Disease | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | HGRF Survival | 12.35 Months |
| Papillary Disease | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 48 months | 32.7 Months |
| Papillary Disease | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 57 months | 32.7 Months |
| Total | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 36 months | 23.6 Months |
| Total | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 57 months | 19.0 Months |
| Total | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | Probability of duration of HGRF survival for 48 months | 21.6 Months |
| Total | Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) | HGRF Survival | 7.31 Months |
Secondary
Durability of Response During the Long-term Follow-up Period.
Durability will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder if clinically indicated.
Time frame: Up to 60 Months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carcinoma in Situ | Durability of Response During the Long-term Follow-up Period. | 48.92 months |
| Papillary Disease | Durability of Response During the Long-term Follow-up Period. | 59.01 months |
| Total | Durability of Response During the Long-term Follow-up Period. | 50.83 months |
Secondary
Incidence of Cystectomy at 12 Months, 2 Years and 5 Years
The incidence of cystectomy is described as the proportion of patients undergoing radical cystectomy for any reason after the first dose, within 12 months, 2 years and 5 years.
Time frame: 60 Months
Population: Proportion of patients undergoing cystectomy within 5 years, 2 years and 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carcinoma in Situ | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 2 years | 35 Participants |
| Carcinoma in Situ | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 12 months | 27 Participants |
| Carcinoma in Situ | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 5 years | 42 Participants |
| Papillary Disease | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 2 years | 10 Participants |
| Papillary Disease | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 12 months | 7 Participants |
| Papillary Disease | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 5 years | 14 Participants |
| Total | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 12 months | 34 Participants |
| Total | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 5 years | 56 Participants |
| Total | Incidence of Cystectomy at 12 Months, 2 Years and 5 Years | 2 years | 45 Participants |
Secondary
Overall Survival Rate in All Patients
Overall survival rate was defined as the time from the first dose to death due to any cause. Patients who were still alive were censored at the last date the patient was known to be alive. Overall survival rate is a Kaplan-Meier estimate of the survivor function at each specific time point. The 95% CI is calculated using the Greenwood's formula with a log-log transformation. Percentage is calculated using the number of patients in the column heading as the denominator.
Time frame: 60 Months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carcinoma in Situ | Overall Survival Rate in All Patients | 6 months | 99 percentage of patients |
| Carcinoma in Situ | Overall Survival Rate in All Patients | 24 months | 94.9 percentage of patients |
| Carcinoma in Situ | Overall Survival Rate in All Patients | 12 months | 98 percentage of patients |
| Carcinoma in Situ | Overall Survival Rate in All Patients | 3 months | 100 percentage of patients |
| Carcinoma in Situ | Overall Survival Rate in All Patients | 60 months | 76.3 percentage of patients |
| Carcinoma in Situ | Overall Survival Rate in All Patients | 48 months | 83.6 percentage of patients |
| Carcinoma in Situ | Overall Survival Rate in All Patients | 9 months | 98 percentage of patients |
| Papillary Disease | Overall Survival Rate in All Patients | 12 months | 97.9 percentage of patients |
| Papillary Disease | Overall Survival Rate in All Patients | 3 months | 100 percentage of patients |
| Papillary Disease | Overall Survival Rate in All Patients | 6 months | 100 percentage of patients |
| Papillary Disease | Overall Survival Rate in All Patients | 9 months | 100 percentage of patients |
| Papillary Disease | Overall Survival Rate in All Patients | 24 months | 93.5 percentage of patients |
| Papillary Disease | Overall Survival Rate in All Patients | 48 months | 88.9 percentage of patients |
| Papillary Disease | Overall Survival Rate in All Patients | 60 months | 85.9 percentage of patients |
| Total | Overall Survival Rate in All Patients | 24 months | 94.5 percentage of patients |
| Total | Overall Survival Rate in All Patients | 6 months | 99.3 percentage of patients |
| Total | Overall Survival Rate in All Patients | 60 months | 79.7 percentage of patients |
| Total | Overall Survival Rate in All Patients | 48 months | 85.4 percentage of patients |
| Total | Overall Survival Rate in All Patients | 12 months | 98 percentage of patients |
| Total | Overall Survival Rate in All Patients | 9 months | 98.6 percentage of patients |
| Total | Overall Survival Rate in All Patients | 3 months | 100 percentage of patients |
Secondary
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS)
Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder. Incidence of HGRF survival at Months 3, 6, 9, and 12, and every 3 months up to Month 24, and then at Months 36, 48, and 57.
Time frame: up to 57 months
Population: A patient was judged to have achieved HGRF survival at a time point (eg, Months 3, 6, 9, and 12) if the patient was alive and without documented recurrence of high-grade disease or muscle-invasive disease progression as assessed by the Investigator at that time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 9 | 28 Participants |
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 3 | 35 Participants |
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 6 | 30 Participants |
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 12 | 21 Participants |
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 24 | 16 Participants |
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 36 | 11 Participants |
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 48 | 7 Participants |
| Carcinoma in Situ | Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) | Month 57 | 7 Participants |
Secondary
Safety of ADSTILADRIN
The type, incidence, relatedness and severity of treatment emergent adverse events of ADSTILADRIN as assessed by NCI-CTCAE V4.03 were monitored.
Time frame: 60 Months
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carcinoma in Situ | Safety of ADSTILADRIN | Serious TEAE | 10 Participants |
| Carcinoma in Situ | Safety of ADSTILADRIN | TEAE | 101 Participants |
| Carcinoma in Situ | Safety of ADSTILADRIN | NCI-CTCAE Grade 3/4/5 TEAE | 22 Participants |
| Papillary Disease | Safety of ADSTILADRIN | Serious TEAE | 9 Participants |
| Papillary Disease | Safety of ADSTILADRIN | TEAE | 45 Participants |
| Papillary Disease | Safety of ADSTILADRIN | NCI-CTCAE Grade 3/4/5 TEAE | 12 Participants |
| Total | Safety of ADSTILADRIN | TEAE | 146 Participants |
| Total | Safety of ADSTILADRIN | NCI-CTCAE Grade 3/4/5 TEAE | 34 Participants |
| Total | Safety of ADSTILADRIN | Serious TEAE | 19 Participants |