A Study to Learn About the Study Medicine PF-08052667 in People With Bladder Cancer

Phase 1RecruitingNCT07206225

Pfizer294 enrolled

Overview

The purpose of this study is to learn how a new medicine called PF-08052667 works when used by itself or together with another medicine called Bacillus Calmette Guerin (BCG), and/or a medicine called sasanlimab. This study is for adults who have a type of bladder cancer that hasn't spread into the muscle layer of the bladder but is more likely to come back or grow. It includes people whose cancer has come back or hasn't gone away after receiving standard treatments like BCG. It may also include people who, based on their doctor's opinion, cannot receive standard treatments or those treatments are not available to them. The study has three parts: * Part 1 (monotherapy dose escalation) will test PF-08052667 as a single-agent at increasing dose levels in participants with certain bladder cancer whose disease has worsened on or after standard treatments. * Part 2 (combination dose escalation) will test PF-08052667 in combination with BCG and/or sasanlimab (fixed dose) in participants with certain bladder cancer whose disease has worsened on or after standard treatments. * Part 3 (dose optimization and expansion) will further test PF-08052667 as a single agent or in combination with BCG and/or sasanlimab, at the dose(s) based on findings from Part 1 and Part 2 in participants with certain bladder cancer including those who has never received standard treatments. All participants will receive the study drug PF-08052667. Only participants in Part 2 and Part 3 of the study will also receive BCG and/or sasanlimab. PF-08052667 will be given as an intravesical infusion, which means it will be injected directly into the bladder. Sasanlimab will be given as a subcutaneous injection, which means it will be injected under the skin. For all parts, treatment with study medicines will continue until either a participant has decided to stop taking part in the study or is asked to leave the study for various reasons or up to about 2 years, whichever occurs first. Duration of trial participation for each participant will vary as long-term follow-up will continue after treatment discontinuation until loss to-follow-up or death, or until the study is stopped by the sponsor.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Interventions

PF-08052667DRUG

PF-08052667 will be administered intravesical (IVe) instillation following a PF-02921367 (DDM) bladder pre-wash

SasanlimabDRUG

Sasanlimab will be administered as subcutaneous (SC) injection

BCGDRUG

BCG will be administered intravesical (IVe) instillation

PF-02921367DRUG

PF-02921367 (DDM) is a 10-min pre- wash and will be administered intravesical (IVe) instillation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

INCLUSION CRITERIA: 1. 18 years of age or older (or the minimum age of consent per local regulations) 2. Histological diagnosis of high-risk, non-muscle invasive urothelial carcinoma of the bladder defined according to the WHO grading system as carcinoma in situ (CIS), with or without concurrent T1/Ta papillary disease. Note: High-grade T1/Ta papillary disease, in the absence of CIS, may be eligible for certain cohorts in Part 2 and 3 3. BCG unresponsive and BCG-exposed cohorts should have persistent or recurrent disease after receiving at least 5 out of 6 doses of the BCG induction therapy. 4. Have refused or are ineligible or not appropriate for radical cystectomy 5. Tissue Requirement: Available tumor tissue within the last 6 months. On-treatment tumor biopsy is optional, unless mandated based on emerging data, or participating in the Biomarker Cohort, or for disease assessment 6. ECOG PS 0 or 1 EXCLUSION CRITERIA: 1. Concomitant anti-cancer therapy for Non-Muscle Invasive Bladder Cancer (NMIBC); and prior radiation therapy to the bladder are not allowed 2. Renal or hepatic impairment; and hematologic abnormalities as defined in the protocol 3. Participants with active, uncontrolled infection as specified in the protocol

Locations (68)

The Kirklin Clinic of UAB Hospital

Birmingham, Alabama, United States

RECRUITING

UAB Infusion Therapy Extended Care Clinic (ECC)

Birmingham, Alabama, United States

RECRUITING

The University of Alabama at Birmingham Investigation Drug Services Pharmacy

Birmingham, Alabama, United States

RECRUITING

University of Alabama at Birmingham

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

Number of participants with dose limiting toxicities (DLTs) in dose escalation in Part 1 and Part 2 participants only

Any AE occurring during the DLT observation period that is attributed to PF-08052667 and not to the underlying disease or other causes is considered a DLT. DLT rate estimated based on data from DLT-evaluable participants during the DLT evaluation period.

Time frame: Day of first dose (Day 1) Up to 21 days

Number of participants with adverse events (AEs) in Part 1 and Part 2 participants only

AEs as characterized by type, frequency, severity (CTCAE v5.0), seriousness, and relatedness to study drug(s).

Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

Number of participants with laboratory abnormalities in Part 1 and Part 2 participants only

Laboratory abnormalities as characterized by type, frequency, severity

Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

Recurrence-free survival (RFS) in Part 3 participants only

RFS is defined as the time from the first dose until recurrence of high-grade disease, or death due to any cause, whichever occurs first

Time frame: Through end of study and up to approximately 2 years

Event-free survival (EFS) in Part 3 participants only

EFS is defined as the time from the first dose until the first occurrence of an EFS event including progressive disease, recurrence of high-grade disease, or death due to any cause, whichever occurs first

Time frame: Through end of study and up to approximately 2 years

Secondary Outcomes

PK: Maximum Observed Serum Concentration (Cmax)

Cmax of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3)

Time frame: From the first day through 30-37 days after the last study treatment

PK: Time to Reach Maximum Observed Serum Concentration (Tmax)

Tmax of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3)

Time frame: From the first day through 30-37 days after the last study treatment

PK: Minimum observed serum concentration (Ctrough)

Ctrough of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3)

Time frame: From the first day through 30-37 days after the last study treatment

PK: Area under the concentration-time curve (AUC) from time zero to last (AUC from time 0 to AUClast)

AUClast of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3)

Time frame: From the first day through 30-37 days after the last study treatment

PK: Half-life (t1/2)

Time frame: From the first day through 30-37 days after the last study treatment

Incidence of Anti-Drug Antibody (ADA): Immunogenicity of PF-08052667 as a single agent (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3)

Incidence and titers of ADA and neutralizing antibody against PF-08052667

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

Duration of Complete Response (CR) in Part 1 and Part 2 participants only

Duration of CR is the time from first documentation of CR until the first occurrence of an Event-free survival (EFS) event

Time frame: Through end of study and up to approximately 2 years

Complete Response Rate (CRR) in Part 1 and Part 2 participants only

CR rate is defined as the proportion of subjects achieving CR

Time frame: Through end of study and up to approximately 2 years

Overall survival (OS) in Part 3 participants only

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause

Time frame: Through end of study approximately 5 years from last participant enrollment

Cystectomy-free survival in all Parts

Cystectomy-free survival is defined as the time from the first dose until cystectomy or death due to any cause, whichever occurs first

Time frame: Through end of study and up to approximately 2 years

Event-free survival (EFS) in Part 1 and Part 2 participants only

Time frame: Through end of study and up to approximately 2 years

Recurrence-free survival (RFS) in Part 1 and Part 2 participants only

RFS is defined as the time from the first dose until recurrence of high-grade disease, or death due to any cause, whichever occurs first

Time frame: Through end of study and up to approximately 2 years

Rate of cystectomy in all parts

Rate of cystectomy is defined as the proportion of participants who had a cystectomy while on study

Time frame: Through end of study and up to approximately 2 years

Number of participants with adverse events (AEs) in Part 3 participants only

AEs as characterized by type, frequency, severity (CTCAE v5.0), seriousness, and relatedness to study drug(s)

Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

Number of participants with laboratory abnormalities in Part3 participants only

Laboratory abnormalities as characterized by type, frequency, severity

Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 2 years

A Study to Learn About the Study Medicine PF-08052667 in People With Bladder Cancer

Overview

Conditions

Interventions

Eligibility

Locations (68)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts