Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Transitional Cell Cancer of the Renal Pelvis and Ureter

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

The Mitomycin C (MMC) concentration of UGN-101 to be used in this trial will be 4 mg MMC per 1 mL of TC-3 gel, maximum dose is 15ml. 6 once weekly intravesical instillations for the ablation treatment.

Treatment with UGN-101 once weekly for a total of 6 times; in a retrograde fashion. Patients who will demonstrate complete response (CR) will be treated with UGN-101 once monthly as a maintenance therapy for a total of 11 instillations or up to the first recurrence whichever comes first.

UGN-101 instillations

Seth Lerner, M.D.

The study is investigating the ability of UroGen's UGN-101 to treat urothelial carcinoma tumors from the upper urinary tract.

Trial TC-UT-03 is a prospective, open label, single-arm trial, designed to assess the efficacy, safety, and tolerability of treatment with UGN-101 instilled in the upper urinary system of patients with non-invasive low-grade (LG), Upper Tract Urothelial Carcinoma (UTUC).

Upon signing of informed consent, the patients will undergo a screening visit for eligibility evaluation. Eligible patients will be treated with UGN-101 once weekly for a total of 6 times; in a retrograde fashion. Patients who will demonstrate complete response (CR) will be treated with UGN-101 once monthly as a maintenance therapy for a total of 11 instillations or up to the first recurrence whichever comes first.

Five (5) weeks (± 1 w) following the last instillation, the Primary Disease Evaluation (PDE) Visit, during which safety and efficacy will be assessed, will take place. During this visit, the ablative effect of the UGN-101 will be assessed visually, by upper tract washed urine cytology, and if there are remaining tumors, by biopsy or brush biopsy if technically feasible.

Patient demonstrating CR at PDE will undergo monthly maintenance instillations of UGN-101 up to 11 months post PDE. Safety follow-up for these patients will be done until one month post last instillation or at the end of the follow-up period in FU visit 12, which is the earlier.

For patients who did not demonstrate Complete Response, to the extent that it is possible, all remaining tumors lesions will be biopsied. The patients shall undergo any additional surgical or other treatment the Principal Investigator (PI) decides deem necessary to remove remaining tumor.

An independent Data Monitoring Committee (DMC) was assigned to this trial. Accumulating safety, tolerability and efficacy data will be monitored periodically by the DMC according to a pre-specified process and frequency detailed in the DMC charter.

The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study

A Phase 3 Multicenter Trial Evaluating the Efficacy and Safety of UGN-101 on Ablation of Upper Urinary Tract Urothelial Carcinoma

Treatment-emergent AEs were most frequently reported from the Renal and urinary disorders system organ class (SOC), 59 (83.1%) patients, as expected, given the underlying indication of low grade (LG) Upper tract urothelial carcinoma (UTUC) in the study population, chemotherapeutic drug in a gel matrix instilled in the upper urinary tract (UUT), and the study procedure of treatment instillation via a ureteral catheter. The toxicity within the upper urinary tract was considered consistent with the disease under study and the mode of administration of UGN-101. Most events in the Renal and urinary disorders SOC were mild to moderate in severity and resolved. No new risks were identified and the overall safety profile was consistent with the known safety profile of endoscopic administration of intravesical mitomycin and of mitomycin. Overall, based on the safety and efficacy results to date, the benefit-risk profile of UGN-101 is favorable for the treatment of LG-UTUC.

The primary efficacy endpoint was the number of patients attaining complete response (CR) at the end of the treatment period (Primary Disease Evaluation (PDE) visit). The CR was defined dichotomously as "Success" if CR was confirmed at PDE visit (or relevant follow-up), and "Failure" otherwise.

Continuously: Duration of CR or time-to-recurrence since the Primary Disease Evaluation (PDE) Visit (i.e., time in days from the visit at which CR was determined until recurrence or censoring). This endpoint served as the main long-term durability endpoint. Dichotomously: "Success" if CR was still present at the 12 month post-PDE Visit (at Follow-Up Visit 4), and "Failure" otherwise. This endpoint served as a supportive long-term durability endpoint.

Durability of CR defined dichotomously as "Success" if CR was achieved at Primary Disease Evaluation (PDE) visit and remained at follow-up Visit 1, Visit 2 and Visit 3 (3, 6, 9 and 12 months post PDE visit), and "Failure" otherwise.

Clinical benefit for patients with partial response (PR) at the PDE visit. Clinical benefit endpoint was analyzed using the Intent-to-Treat (ITT) Analysis Set, including patients who achieved partial response at PDE Visit.Partial response at PDE visit will be defined dichotomously, similarly to the primary efficacy endpoint. For subjects with partial response at PDE visit, originally planned and actual treatments will be compared.

Cmax: maximum plasma concentration

Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., \< 0.100 ng/mL). The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL). The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.

Tmax: time to maximum plasma concentration

Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., \< 0.100 ng/mL).

The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL), and the Tmax was 1.79 hours (range: 0.50 to 5.17 hours) after instillation. The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.

Half-life (t½): terminal half-life

The mean apparent t½ following instillation of mitomycin into the upper urinary tract (UUT) was 1.27 hours (76 minutes), which was longer than the true t½ of mitomycin following a 30 mg bolus injection (mean t½ value of approximately 17 minutes). The apparent t½ demonstrates that UGN-101 dissolved gradually, resulting in prolonged exposure of mitomycin following local instillation into the UUT.

UroGen Pharma Ltd.

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed Low Grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the Primary Disease Evaluation (PDE) Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen.

UGN-101 Mitomycin for Pyelocalyceal Solution

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the UUT. Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed LG noninvasive UTUC were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen.

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Israel

Region of Enrollment

Madlen Malinowski

The Primary Efficacy Endpoint Was the Number of Patients Attaining Complete Response (CR) at the End of the Treatment Period (PDE Visit).

Population was analyzed at 12 months post Primary Disease Evaluation (PDE) visit. 8 out of 41 patients had disease recurrence. The Kaplan-Meier estimate of 12 month duration of complete response (CR) rate was 82%.

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen.

The Key Secondary Efficacy Endpoint Was Long-term Durability of Complete Response (CR): Number of Patients Who Maintained CR at 12 Month Post PDE Visit. This Endpoint Was Defined Only for Those Patients Who Achieved CR at the PDE Visit.

Patients reaching CR at PDE evaluated at 3 months post PDE

UGN-101 Patients Evaluated 3 Months Post PDE

Patients reaching CR at PDE evaluated at 6 months post PDE

UGN-101 Patients Evaluated at 6 Months Post PDE

Patients reaching CR at PDE evaluated at 9 months post PDE

UGN-101 Patients Evaluated at 9 Months Post PDE

Patients reaching CR at PDE evaluated at 12 months post PDE

UGN-101 Patients Evaluated at 12 Months Post PDE

Durability of Complete Response (CR) for Each Follow-up Time Point.

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the UUT.

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed LG noninvasive UTUC were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen.

Clinical Benefit for Patients With Partial Response (PR) at the Primary Disease Evaluation (PDE) Visit. Clinical Benefit Endpoint Was Analyzed Using the Intent-to-Treat (ITT) Analysis Set, Including Patients Who Achieved Partial Response at PDE Visit.

The PK profiles of the first UGN-101 instillation in the blood were to be examined for the first 6 patients.

Pharmacokinetic Population

PK Analysis Set: Consisted of patients who signed consent for PK and had sufficient PK data for the determination of PK parameters.

Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients.

Treatment-emergent Adverse Events (TEAEs)

TEAEs related to study drug

TEAEs related to study procedure

TEAEs related to study drug or preocedure

Serious Adverse Events (SAE)

SAEs related to study drug or procedure

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen.

Safety: Consisted of all patients who enrolled in the study and received at least 1 instillation of UGN-101.

Safety Adverse Event Outcomes: Safety Was Monitored Throughout the Study by Reviewing Adverse Events (AEs).

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the Primary Disease Evaluation (PDE) Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen.

Overall Study

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Urologic Neoplasms

Urogenital Neoplasms

Disease Attributes

Pharmaceutical Solutions

The dose of Jelmyto to be instilled is 4 mg per mL via ureteral catheter or a nephrostomy tube, with total instillation volume based on volumetric measurements using pyelography, not to exceed 15 mL (60 mg of mitomycin).

Instill Jelmyto once weekly for six weeks. For patients with a complete response 3 months after Jelmyto initiation, Jelmyto instillations may be administered once a month for a maximum of 11 additional instillations.

Jelmyto (mitomycin) for pyelocalyceal solution

Anthony Fernandez, PharmD

Brett Johnson, MD

Yair Lotan, MD

The purpose of this registry is to evaluate real world experience and outcomes of patients with Upper Tract Urothelial Cancer (UTUC) treated with Jelmyto in the United States.

Patients may be enrolled prospectively, at the time of receiving Jelmyto, or after receiving Jelmyto for retrospective data capture and prospective follow up. Patients will be followed until 3 years after the first dose of Jelmyto or death.

Data will be captured to address specific clinical questions and data gaps related to real world use of Jelmyto.

Example clinical questions:

1. How is Jelmyto used in the real world setting?
2. What adverse events (AEs) and at what rates and time points are they observed in the real world setting?
3. What is the disease volume before and after resection/ablation prior to treating with Jelmyto?
4. Did the use of Jelmyto impact clinical decision making and management?
5. What is the complete response (CR) rate, duration of response, and rate of progression, including subgroups of interest?
6. What are the rates of, time to, and pathology at radical nephroureterectomy (RNU) by response to treatment and number of Jelmyto doses received?
7. What are outcomes for non-responders or partial responders? What are the rates of surgical and therapeutic treatment options received following response assessment, including additional Jelmyto?
8. What was the outcome of patients with solitary kidney and/or chronic kidney disease (CKD)? Did Jelmyto prevent dialysis by avoiding nephrectomy in solitary kidney or in patients with baseline CKD?
9. What is the rate and timing of bladder cancer occurrence and/or recurrences?

uTRACT Jelmyto Registry: A Registry of Patients With Upper Tract Urothelial Cancer (UTUC) Treated With Jelmyto

uTRACT Jelmyto Registry: A Multicenter, Prospective and Retrospective Registry to Evaluate Real World Experience and Outcomes of Patients With Upper Tract Urothelial Cancer (UTUC) Treated With Jelmyto

The Mitomycin C (MMC) concentration of UGN-101 to be used in this trial will be 4 mg MMC per 1 mL of TC-3 gel, the maximum dose is 15ml. 3-6 once weekly intravesical instillations for the ablation treatment.

Treatment with UGN-101 once weekly for a total of 3-6 times; in a retrograde fashion.

Ifat Klein, Phd

This trial is designed to evaluate the efficacy and safety of UGN-101 administered to the upper urinary tract (UUT) in patients who were treated in Trial TC-UT-03, found to be a complete response (CR) at the Primary Disease Evaluation (PDE) 1 Visit and are subsequently found to have a documented recurrence of low grade (LG) upper tract urothelial carcinoma (UTUC) at follow up (FU).

This is an open-label, single-arm, Phase 3b multicenter extension trial, designed to evaluate the efficacy and safety of UGN-101 administered to the UUT in patients who were treated in Trial TC-UT-03, found to be a CR at the PDE 1 Visit, and are subsequently found to have a documented recurrence of LG UTUC at FU.

Upon signing of informed consent, the patients will undergo their routine ureteroscopy to assess durability. A biopsy will be performed at Visit 0, if appropriate, to confirm evidence of tumor. If a high grade (HG) UTUC is confirmed by biopsy and/or cytology, the patient will be excluded from the retreatment trial. Eligible patients with confirmed LG non-invasive UTUC will be treated with 3 to 6 once-weekly instillations of UGN-101 in a retrograde fashion, per investigator's discretion.

Five weeks (± 1 week) following the last Investigational product (IP) treatment, the patient will be assessed for efficacy and safety at the PDE 2 Visit. At this visit, the patient will undergo ureteroscopy and any remaining lesions will be biopsied, and UUT urine wash will be collected for cytology.

Patients demonstrating CR at the PDE 2 Visit will undergo FU visits at 3, 6, 9, and 12 months (± 2 weeks) following the PDE 2 Visit.

The trial will be approximately 15 months, per patient: a 3- to 6-week treatment period, followed by 4 to 6 weeks post-treatment leading up to the PDE 2 Visit, and a 12-month FU post PDE 2 Visit. This trial will follow the Steering Committee, and a Data Monitoring Committee (DMC) has been assigned as established for the primary trial TC-UT-03.

Efficacy and Safety of UGN-101 in Recurrent Patients

A Phase 3b Multicenter Extension Trial Evaluating the Efficacy and Safety of UGN-101 (Mitomycin Gel) for Instillation on Ablation of Upper Urinary Tract Urothelial Carcinoma in Recurrent Patients From Trial TC-UT-03

Adverse events (AEs) analyses will include only Treatment Emergent Adverse Events (TEAEs), namely, those events which started on the day of first trial IP administration or afterwards.

The incidence (no. of patients) of TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary;

* Breakdowns of TEAEs by all AEs attributes will also be provided;
* Breakdowns of TEAEs by age, sex and volume of instillation will also be provided;
* The incidence of serious TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary as well as by serious adverse events (SAEs) attributes and by age, sex, and volume of instillation. SAEs will also be listed.

Adverse events (AEs) analyses will include only Treatment Emergent Adverse Events (TEAEs), namely, those events which started on the day of first trial IP administration or afterwards.

The Frequency (no. of patients) of TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary;

* Breakdowns of TEAEs by all AEs attributes will also be provided;
* Breakdowns of TEAEs by age, sex and volume of instillation will also be provided;
* The Frequency of serious TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary as well as by serious adverse events (SAEs) attributes and by age, sex, and volume of instillation. SAEs will also be listed.

Changes from baseline in laboratory values and incidence of measurements defined as Potentially Clinically Significant (PCS) will include the following:

Complete blood count (CBC, including red blood, cell indices, and white blood cell differential, Platelet count), Creatinine, Blood urea nitrogen, Uric acid, Sodium, Potassium, Phosphorus, Calcium, serum glutamate oxaloacetate transaminase/aspartate aminotransferase (SGOT/AST), serum glutamate pyruvate transaminase/Alanine transaminase (SGPT/ALT), gamma-glutamyl transferase (GGT), Alkaline phosphatase, Total Bilirubin, Direct Bilirubin, Albumin, Total protein, Prothrombin Time and International Normalized Ratio, and Urinalysis (Specific gravity, power of hydrogen (pH), Glucose, Urobilinogen, Bilirubin, Blood, Protein, Nitrites, Leukocyte Esterase, Microscopic examination, Bacteriuria (if required) and White blood cells)

Changes from baseline in vital signs assessments values and incidence of measurements of Potential Clinical Significance (PCS) will include blood pressure, pulse, and temperature

Any clinically-relevant changes occurring during the trial visit will be recorded in the AE sections of the case report form (CRF). Full general physical examination will be done on visits 0, 7, and 11 Urology-oriented physical examinations will be done on visits 0, 7, 8, 9, 10, and 11.

Full physical examination findings are composite outcome measure consisting of multiple measures:

General appearance, Cardiovascular system, Respiratory system, HEENT (head, eyes, ears, nose, and throat) and neck, Abdomen Extremities and Neurologic system Skin

Urology-Oriented physical examination findings are composite outcome measure consisting of multiple measures:

Urethral meatus, Perineal skin and mucus membranes Scrotum and testes (for male patients), Lymphadenopathy, Rectal examination (Screening visit only) Bimanual examination (female patients - Screening visit only)

Complete response defined dichotomously as "Success" if CR was confirmed at the end of the treatment period (PDE 2 Visit), and "Failure" otherwise.

This endpoint is defined only for those patients demonstrating CR at the PDE 2 Visit.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study	NCT02793128	Carcinoma, Tran... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.
uTRACT Jelmyto Registry: A Registry of Patients With Upper Tract Urothelial Cancer (UTUC) Treated With Jelmyto	NCT05874921	Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Carc... Urothelial Canc... Urothelial Carc... Carcinoma, Tran... Transitional Ce...	Jelmyto (mitomy...	18 Years -	UroGen Pharma Ltd.
The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study	NCT02793128	Carcinoma, Tran... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.
Efficacy and Safety of UGN-101 in Recurrent Patients	NCT04006691	Carcinoma Transitional Ce... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.

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