PF-07225570 Alone or in Combination With an Anti-PD-1 Antibody in Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)
- Conditions
- Bladder Cancer
- Interventions
- Drug: PF-07225570Drug: sasanlimab
- Registration Number
- NCT05259397
- Lead Sponsor
- Pfizer
- Brief Summary
The primary objective of this study is to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of PF-07225570 alone or in combination with an anti-PD-1 antibody in participants with recurrent non-muscle invasive bladder cancer. This study consists of 2 parts, single agent dose escalation (Part 1A), dose finding of PF-07225570 in combination with anti-PD-1 antibody (Part 1B) and dose expansion (Part 2).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Histological confirmed and documented diagnosis of non-muscle invasive urothelial carcinoma
Participants with recurrent non-muscle invasive bladder cancer (intermediate risk or high risk)
Ineligible for or elected not to undergo radical cystectomy
No evidence of upper tract urothelial cancer or cancer within the prostatic urethra as documented by imaging studies performed within 6 months of enrollment
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Adequate bone marrow, renal and liver function
Evidence of muscle-invasive, locally advanced or metastatic urothelial carcinoma or concurrent extravesical, non-muscle invasive urothelial carcinoma
Macroscopic hematuria, traumatic catheterization or active urinary tract infection
Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent
Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) Hepatitis B, Hepatitis C, and known Human Immunodeficiency Virus infection or Acquired Immunodeficiency Syndrome-related illness
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2A PF-07225570 monotherapy PF-07225570 IVe Single Agent Dose Expansion Part 1B PF-07225570 and sasanlimab PF-07225570 PF-07225570 IVe and sasanlimab Subcutaneous (SQ) Combination Dose Escalation Part 1A PF-07225570 monotherapy PF-07225570 Intravesical (IVe) Single Agent Dose Escalation Part 2B PF-07225570 and sasanlimab PF-07225570 PF-07225570 IVe and sasanlimab SQ Combination Dose Expansion Part 2B PF-07225570 and sasanlimab sasanlimab PF-07225570 IVe and sasanlimab SQ Combination Dose Expansion Part 1B PF-07225570 and sasanlimab sasanlimab PF-07225570 IVe and sasanlimab Subcutaneous (SQ) Combination Dose Escalation
- Primary Outcome Measures
Name Time Method Number of participants with Dose limiting toxicities Baseline up to 28 days Number of Participants with Adverse Events (AEs) according to Severity Baseline up to approximately 24 months Number of Participants with AEs according to Seriousness Baseline up to approximately 24 months Number of Participants with AEs according to Relationship Baseline up to approximately 24 months
- Secondary Outcome Measures
Name Time Method Urine PF-07225570 concentration after a single dose Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0-2 hours, and 4 - 6 hours post-instillation on Cycle 1 Day 1 Durability of complete responses (CRs) as measured from time of documented CR to time of high-grade tumor recurrence, disease progression, or death (whichever occurs first) in participants who achieved a CR Baseline up to 24 months Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07225570 after a single dose Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0.5, 1, 2, 3, 4, 6 and 24 hours after instillation Concentration from maximum to steady state (Cmax,ss) of PF-07225570 after multiple doses Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation Incidence of Radical Cystectomy Baseline up to 24 months Serum sasanlimab concentrations Pre-dose (within 6 hours) before each administration For participants with high-grade Ta/ T1 disease only, Proportion of participants without high-grade-recurrence at each assessment visit. Baseline up to 24 months Ta is defined as the stage of bladder cancer as a non-invasive papillary carcinoma. T1 is defined as the stage of cancer in which the cancer cells are only growing in the most superficial layer of tissues and have not grown into deeper tissues; in bladder cancer, T1 is defined as an invasion into the lamina propria without invasion into the muscularis propria
Area under the curve from specified time to steady state (AUCτ,ss) of PF-07225570 after multiple doses Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation Progression-Free Survival Baseline up to 24 months Proportion of participants with carcinoma in situ (CIS) achieving complete response at any time after first dose of PF 07225570 Baseline up to 24 months Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07225570 after a single dose Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0.5, 1, 2, 3, 4, 6 and 24 hours after instillation Urine PF-07225570 concentration after multiple doses Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0-2 hours and 2 - 4 hours post-instillation. Incidence and titers of neutralizing antibodies (NAb) against sasanlimab Pre-dose (within 6 hours) before each administration Maximum Observed Plasma Concentration (Cmax) of PF-7225570 after a single dose Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0.5, 1, 2, 3, 4, 6 and 24 hours after instillation Time from maximum concentration to steady state (Tmax,ss) of PF-07225570 after multiple doses Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation Overall survival Baseline up to 3 years Incidence and titers of anti-drug antibodies (ADA) against sasanlimab Pre-dose (within 6 hours) before each administration
Trial Locations
- Locations (4)
Szpital Specjalistyczny im. Sw. Rodziny SPZOZ
🇵🇱Warszawa, Poland
Medical Concierge Centrum Medyczne
🇵🇱Warszawa, Poland
Columbia University Medical Center - Herbert Irving Pavilion
🇺🇸New York, New York, United States
CUMC Research Pharmacy
🇺🇸New York, New York, United States