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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: PF-07225570; Drug: sasanlimab

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Warszawa, Poland, 02-798
    • Medical Concierge Centrum Medyczne
  • Warszawa, Poland, 02-544
    • Szpital Specjalistyczny im. Sw. Rodziny SPZOZ
• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Herbert Irving Pavilion
    • New York, New York, United States, 10032
      • CUMC Research Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 24, 2022
• Primary Completion (ANTICIPATED): March 15, 2027
• Study Completion (ANTICIPATED): April 13, 2028

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (ACTUAL): February 28, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Urothelial cancer; Recurrent Non-Muscle Invasive Bladder Cancer (NMIBC); Toll-like receptor 7 (TLR7); Toll-like receptor 8 (TLR8)
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: C4661001; 2021-005858-28 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No