PF-07225570 Alone or in Combination With an Anti-PD-1 Antibody in Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: PF-07225570
* Drug: sasanlimab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A PF-07225570 monotherapy<br>Intravesical (IVe) Single Agent Dose Escalation | Drug: PF-07225570<br>* PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.<br>|
| Experimental: Part 1B PF-07225570 and sasanlimab<br>PF-07225570 IVe and sasanlimab Subcutaneous (SQ) Combination Dose Escalation | Drug: PF-07225570<br>* PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.<br>Drug: sasanlimab<br>* Sasanlimab will be administered SQ on day 1 of each 28 day cycle.<br>* Other names: anti-PD-1 (programmed cell death protein-1) antibody;|
| Experimental: Part 2A PF-07225570 monotherapy<br>IVe Single Agent Dose Expansion | Drug: PF-07225570<br>* PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.<br>|
| Experimental: Part 2B PF-07225570 and sasanlimab<br>PF-07225570 IVe and sasanlimab SQ Combination Dose Expansion | Drug: PF-07225570<br>* PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.<br>Drug: sasanlimab<br>* Sasanlimab will be administered SQ on day 1 of each 28 day cycle.<br>* Other names: anti-PD-1 (programmed cell death protein-1) antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| For participants with high-grade Ta/ T1 disease only, Proportion of participants without high-grade-recurrence at each assessment visit. | 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 | Baseline up to 24 months | 
| 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 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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. | 
| Progression-Free Survival |  | Baseline up to 24 months | 
| Incidence of Radical Cystectomy |  | Baseline up to 24 months | 
| Overall survival |  | Baseline up to 3 years | 
| Serum sasanlimab concentrations |  | Pre-dose (within 6 hours) before each administration | 
| Incidence and titers of neutralizing antibodies (NAb) against sasanlimab |  | Pre-dose (within 6 hours) before each administration | 
| Incidence and titers of anti-drug antibodies (ADA) against sasanlimab |  | Pre-dose (within 6 hours) before each administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Non-Muscle Invasive Bladder Cancer (NMIBC), Urothelial cancer, Toll-like receptor 7 (TLR7), Toll-like receptor 8 (TLR8)