Clinical trial NCT05259397: PF-07225570 Alone or in Combination With an Anti-PD-1 Antibody in Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)
Official title: A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-07225570 EITHER ALONE OR IN COMBINATION WITH AN ANTI-PD-1 ANTIBODY, IN PARTICIPANTS WITH RECURRENT NON-MUSCLE INVASIVE BLADDER CANCER
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Bladder Cancer
Keywords: Recurrent Non-Muscle Invasive Bladder Cancer (NMIBC)
Urothelial cancer
Toll-like receptor 7 (TLR7)
Toll-like receptor 8 (TLR8)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-02-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Number of participants with Dose limiting toxicities
timeFrame: Baseline up to 28 days
measure: Number of Participants with Adverse Events (AEs) according to Severity
timeFrame: Baseline up to approximately 24 months
measure: Number of Participants with AEs according to Seriousness
timeFrame: Baseline up to approximately 24 months
measure: Number of Participants with AEs according to Relationship
timeFrame: Baseline up to approximately 24 months
Secondary outcomes:
measure: Proportion of participants with carcinoma in situ (CIS) achieving complete response at any time after first dose of PF 07225570
timeFrame: Baseline up to 24 months
measure: 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
timeFrame: Baseline up to 24 months
measure: For participants with high-grade Ta/ T1 disease only, Proportion of participants without high-grade-recurrence at each assessment visit.
timeFrame: Baseline up to 24 months
measure: Maximum Observed Plasma Concentration (Cmax) of PF-7225570 after a single dose
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07225570 after a single dose
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07225570 after a single dose
timeFrame: 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
measure: Concentration from maximum to steady state (Cmax,ss) of PF-07225570 after multiple doses
timeFrame: Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation
measure: Time from maximum concentration to steady state (Tmax,ss) of PF-07225570 after multiple doses
timeFrame: Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation
measure: Area under the curve from specified time to steady state (AUCτ,ss) of PF-07225570 after multiple doses
timeFrame: Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation
measure: Urine PF-07225570 concentration after a single dose
timeFrame: 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
measure: Urine PF-07225570 concentration after multiple doses
timeFrame: Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0-2 hours and 2 - 4 hours post-instillation.
measure: Progression-Free Survival
timeFrame: Baseline up to 24 months
measure: Incidence of Radical Cystectomy
timeFrame: Baseline up to 24 months
measure: Overall survival
timeFrame: Baseline up to 3 years
measure: Serum sasanlimab concentrations
timeFrame: Pre-dose (within 6 hours) before each administration
measure: Incidence and titers of neutralizing antibodies (NAb) against sasanlimab
timeFrame: Pre-dose (within 6 hours) before each administration
measure: Incidence and titers of anti-drug antibodies (ADA) against sasanlimab
timeFrame: Pre-dose (within 6 hours) before each administration
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: New York
country: United States
facility: CUMC Research Pharmacy
state: New York
city: Warszawa
country: Poland
facility: Szpital Specjalistyczny im. Sw. Rodziny SPZOZ
city: Warszawa
country: Poland
facility: Medical Concierge Centrum Medyczne
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: