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

Primary Purpose

Bladder Cancer

Status

Withdrawn

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

PF-07225570

sasanlimab

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring Recurrent Non-Muscle Invasive Bladder Cancer (NMIBC), Urothelial cancer, Toll-like receptor 7 (TLR7), Toll-like receptor 8 (TLR8)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Columbia University Medical Center - Herbert Irving Pavilion
CUMC Research Pharmacy
Szpital Specjalistyczny im. Sw. Rodziny SPZOZ
Medical Concierge Centrum Medyczne

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part 1A PF-07225570 monotherapy

Part 1B PF-07225570 and sasanlimab

Part 2A PF-07225570 monotherapy

Part 2B PF-07225570 and sasanlimab

Arm Description

Intravesical (IVe) Single Agent Dose Escalation

PF-07225570 IVe and sasanlimab Subcutaneous (SQ) Combination Dose Escalation

IVe Single Agent Dose Expansion

PF-07225570 IVe and sasanlimab SQ Combination Dose Expansion

Outcomes

Primary Outcome Measures

Number of participants with Dose limiting toxicities

Number of Participants with Adverse Events (AEs) according to Severity

Number of Participants with AEs according to Seriousness

Number of Participants with AEs according to Relationship

Secondary Outcome Measures

Proportion of participants with carcinoma in situ (CIS) achieving complete response at any time after first dose of PF 07225570

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

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

Maximum Observed Plasma Concentration (Cmax) of PF-7225570 after a single dose

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07225570 after a single dose

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07225570 after a single dose

Concentration from maximum to steady state (Cmax,ss) of PF-07225570 after multiple doses

Time from maximum concentration to steady state (Tmax,ss) of PF-07225570 after multiple doses

Area under the curve from specified time to steady state (AUCτ,ss) of PF-07225570 after multiple doses

Urine PF-07225570 concentration after a single dose

Urine PF-07225570 concentration after multiple doses

Progression-Free Survival

Incidence of Radical Cystectomy

Overall survival

Serum sasanlimab concentrations

Incidence and titers of neutralizing antibodies (NAb) against sasanlimab

Incidence and titers of anti-drug antibodies (ADA) against sasanlimab

Full Information

NCT ID

NCT05259397

First Posted

February 15, 2022

Last Updated

March 7, 2023

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT05259397

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Pfizer has decided to terminate Study C4661001 due to strategic considerations. This decision is not due to any specific safety reasons or requests from any regulatory authorities. No participants have been enrolled in this study.

Study Start Date

March 24, 2022 (Actual)

Primary Completion Date

September 19, 2022 (Actual)

Study Completion Date

September 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bladder Cancer

Keywords

Recurrent Non-Muscle Invasive Bladder Cancer (NMIBC), Urothelial cancer, Toll-like receptor 7 (TLR7), Toll-like receptor 8 (TLR8)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1A PF-07225570 monotherapy

Arm Type

Experimental

Arm Description

Intravesical (IVe) Single Agent Dose Escalation

Arm Title

Part 1B PF-07225570 and sasanlimab

Arm Type

Experimental

Arm Description

PF-07225570 IVe and sasanlimab Subcutaneous (SQ) Combination Dose Escalation

Arm Title

Part 2A PF-07225570 monotherapy

Arm Type

Experimental

Arm Description

IVe Single Agent Dose Expansion

Arm Title

Part 2B PF-07225570 and sasanlimab

Arm Type

Experimental

Arm Description

PF-07225570 IVe and sasanlimab SQ Combination Dose Expansion

Intervention Type

Drug

Intervention Name(s)

PF-07225570

Intervention Description

PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.

Intervention Type

Drug

Intervention Name(s)

sasanlimab

Other Intervention Name(s)

anti-PD-1 (programmed cell death protein-1) antibody

Intervention Description

Sasanlimab will be administered SQ on day 1 of each 28 day cycle.

Primary Outcome Measure Information:

Title

Number of participants with Dose limiting toxicities

Time Frame

Baseline up to 28 days

Title

Number of Participants with Adverse Events (AEs) according to Severity

Time Frame

Baseline up to approximately 24 months

Title

Number of Participants with AEs according to Seriousness

Time Frame

Baseline up to approximately 24 months

Title

Number of Participants with AEs according to Relationship

Time Frame

Baseline up to approximately 24 months

Secondary Outcome Measure Information:

Title

Proportion of participants with carcinoma in situ (CIS) achieving complete response at any time after first dose of PF 07225570

Time Frame

Baseline up to 24 months

Title

Time Frame

Baseline up to 24 months

Title

For participants with high-grade Ta/ T1 disease only, Proportion of participants without high-grade-recurrence at each assessment visit.

Description

Time Frame

Baseline up to 24 months

Title

Maximum Observed Plasma Concentration (Cmax) of PF-7225570 after a single dose

Time Frame

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

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07225570 after a single dose

Time Frame

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

Title

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07225570 after a single dose

Time Frame

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

Title

Concentration from maximum to steady state (Cmax,ss) of PF-07225570 after multiple doses

Time Frame

Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation

Title

Time from maximum concentration to steady state (Tmax,ss) of PF-07225570 after multiple doses

Time Frame

Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation

Title

Area under the curve from specified time to steady state (AUCτ,ss) of PF-07225570 after multiple doses

Time Frame

Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation

Title

Urine PF-07225570 concentration after a single dose

Time Frame

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

Title

Urine PF-07225570 concentration after multiple doses

Time Frame

Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0-2 hours and 2 - 4 hours post-instillation.

Title

Progression-Free Survival

Time Frame

Baseline up to 24 months

Title

Incidence of Radical Cystectomy

Time Frame

Baseline up to 24 months

Title

Overall survival

Time Frame

Baseline up to 3 years

Title

Serum sasanlimab concentrations

Time Frame

Pre-dose (within 6 hours) before each administration

Title

Incidence and titers of neutralizing antibodies (NAb) against sasanlimab

Time Frame

Pre-dose (within 6 hours) before each administration

Title

Incidence and titers of anti-drug antibodies (ADA) against sasanlimab

Time Frame

Pre-dose (within 6 hours) before each administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Columbia University Medical Center - Herbert Irving Pavilion

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

CUMC Research Pharmacy

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Szpital Specjalistyczny im. Sw. Rodziny SPZOZ

City

Warszawa

ZIP/Postal Code

02-544

Country

Poland

Facility Name

Medical Concierge Centrum Medyczne

City

Warszawa

ZIP/Postal Code

02-798

Country

Poland

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing 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.

Links:

URL

https://pmiform.com/clinical-trial-info-request?StudyID=C4661001

Description

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Learn more about this trial

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

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