A Phase 1 Dose-escalation Study of UGN-301 in Patients With Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)
- Conditions
- Non-muscle Invasive Bladder Cancer
- Interventions
- Registration Number
- 2023-508404-37-00
- Lead Sponsor
- Urogen Pharma Ltd.
- Brief Summary
This study is being conducted to evaluate the safety and determine the recommended Phase 2 dose (RP2D) of UGN-301 (zalifrelimab) administered intravesically as monotherapy and in combination with other agents in patients with recurrent NMIBC.
- Detailed Description
This master protocol will comprise multiple treatment arms designed to independently investigate intravesical delivery of UGN-301 either as monotherapy or in combination with other agents. Initial study treatment arms will include:
* UGN-301 monotherapy
* UGN-301 + UGN-201 (imiquimod) in combination
* UGN-301 + gemcitabine in combination
Additional study treatment arms investigating UGN-301 in combination with other agents may be added in the future.
The study will evaluate escalating doses of UGN-301 to determine the biologically effective dose (BED) and maximum tolerated dose (MTD) of UGN-301 either as monotherapy or in combination with other agents.
When evaluated in combination with other agents, the UGN-301 dose will begin at least 1 dose level lower than the highest dose level cleared in the monotherapy arm, or 1 dose level lower than the RP2D.
Eligible patients in each study treatment arm will enter a 12-week Induction Period.
Patients with noninvasive papillary carcinoma and/or tumor that invades the lamina propria (Ta and/or T1) who do not have disease recurrence and patients with carcinoma in situ (CIS) who have a complete response (CR) at 3 months after the start of treatment will return to the clinic for a Safety Follow-up Visit at 6 months after the start of treatment.
Ta/T1 patients without disease recurrence and CIS patients with CR at 6 months may enter an Optional Maintenance Period of up to 9 months.
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description UGN-301 monotherapy dose escalation (Arm A) UGN-301 Dose escalation of UGN-301 monotherapy in patients with recurrent NMIBC with high grade (HG) Ta and/or T1 disease and/or CIS or recurrent intermediate risk (IR) low grade (LG) Ta and/or T1 disease. UGN-301 dose escalation + UGN-201 combination (Arm B) UGN-201 Dose escalation of UGN-301 in combination with a fixed dose of UGN-201 in patients with recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. UGN-301 dose escalation + gemcitabine combination (Arm C) UGN-301 Dose escalation of UGN-301 in combination with a fixed dose of gemcitabine in patients with recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. UGN-301 dose escalation + UGN-201 combination (Arm B) UGN-301 Dose escalation of UGN-301 in combination with a fixed dose of UGN-201 in patients with recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. UGN-301 dose escalation + gemcitabine combination (Arm C) Gemcitabine Dose escalation of UGN-301 in combination with a fixed dose of gemcitabine in patients with recurrent NMIBC with HG Ta and/or T1 disease and/or CIS.
- Primary Outcome Measures
Name Time Method Recurrence-free survival (RFS) rate 3 months RFS rate is defined as the proportion of patients with Ta/T1 disease who are recurrence-free at the Week 12 (3-month) Visit.
Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) Up to 15 months The number of patients with each type of event will be summarized.
Complete response rate (CRR) 3 months CRR is defined as the proportion of CIS patients who achieved CR at the Week 12 (3-month) Visit.
Concentration of UGN-301 in blood and urine 6 weeks Data will be summarized using descriptive statistics.
- Secondary Outcome Measures
Name Time Method UGN-301 concentration in serum at the end of a dosing interval (Ctau) following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
UGN-201 t1/2 following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
UGN-301 area under the concentration-time curve (AUC) following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
UGN-301 terminal half-life (t1/2) following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
Concentration of UGN-201 and its metabolites in blood and urine 6 weeks Data will be summarized using descriptive statistics.
UGN-201 Cmax following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
UGN-301 maximum serum concentration (Cmax) following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
Presence of anti-drug antibodies (ADA) in serum 3 months The number of patients with ADA will be summarized.
UGN-301 time to maximum serum concentration (tmax) following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
UGN-201 Ctau following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
UGN-201 AUC following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
UGN-201 tmax following single and repeat dose administration 6 weeks Data will be summarized using descriptive statistics.
Trial Locations
- Locations (7)
IRCCS Istituto Nazionale Tumori Fondazione Pascale
🇮🇹Naples, Italy
Ospedale San Raffaele S.r.l.
🇮🇹Milan, Italy
Hospital Universitario Hm Sanchinarro
🇪🇸Madrid, Spain
Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
Hospital Clinic De Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Pozuelo De Alarcon, Spain
Istituto Oncologico Veneto
🇮🇹Padova, Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale🇮🇹Naples, ItalyPaolo Antonio AsciertoSite contact390815903699p.ascierto@istitutotumori.na.it