Non-muscle Invasive Bladder Cancer
Conditions
Keywords
NMIBC, Non-Muscle Invasive Bladder Cancer, Bladder Cancer, Bladder Tumors, Bladder Neoplasms, Malignant Tumor of Urinary Bladder, Urinary Bladder Cancer, Cancer of Bladder
Brief summary
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.
Interventions
DRUGPF-08052667
PF-08052667 will be administered intravesical (IVe) instillation following a PF-02921367 (DDM) bladder pre-wash
DRUGSasanlimab
Sasanlimab will be administered as subcutaneous (SC) injection
DRUGBCG
BCG will be administered intravesical (IVe) instillation
DRUGPF-02921367
PF-02921367 (DDM) is a 10-min pre- wash and will be administered intravesical (IVe) instillation
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with dose limiting toxicities (DLTs) in dose escalation in Part 1 and Part 2 participants only | Day of first dose (Day 1) Up to 21 days | 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. |
| Number of participants with adverse events (AEs) in Part 1 and Part 2 participants only | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | AEs as characterized by type, frequency, severity (CTCAE v5.0), seriousness, and relatedness to study drug(s). |
| Number of participants with laboratory abnormalities in Part 1 and Part 2 participants only | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Laboratory abnormalities as characterized by type, frequency, severity |
| Recurrence-free survival (RFS) in Part 3 participants only | Through end of study and up to approximately 2 years | 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 |
| Event-free survival (EFS) in Part 3 participants only | Through end of study and up to approximately 2 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Maximum Observed Serum Concentration (Cmax) | From the first day through 30-37 days after the last study treatment | Cmax of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3) |
| PK: Time to Reach Maximum Observed Serum Concentration (Tmax) | From the first day through 30-37 days after the last study treatment | Tmax of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3) |
| PK: Minimum observed serum concentration (Ctrough) | From the first day through 30-37 days after the last study treatment | Ctrough of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3) |
| PK: Area under the concentration-time curve (AUC) from time zero to last (AUC from time 0 to AUClast) | From the first day through 30-37 days after the last study treatment | AUClast of PF-08052667as a monotherapy (Part 1) and in combination with BCG and/or sasanlimab (Part 2 and Part 3) |
| PK: Half-life (t1/2) | 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) | Through 30-37 days after the last study treatment, up to approximately 2 years | Incidence and titers of ADA and neutralizing antibody against PF-08052667 |
| Duration of Complete Response (CR) in Part 1 and Part 2 participants only | Through end of study and up to approximately 2 years | Duration of CR is the time from first documentation of CR until the first occurrence of an Event-free survival (EFS) event |
| Complete Response Rate (CRR) in Part 1 and Part 2 participants only | Through end of study and up to approximately 2 years | CR rate is defined as the proportion of subjects achieving CR |
| Overall survival (OS) in Part 3 participants only | Through end of study approximately 5 years from last participant enrollment | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause |
| Cystectomy-free survival in all Parts | Through end of study and up to approximately 2 years | Cystectomy-free survival is defined as the time from the first dose until cystectomy or death due to any cause, whichever occurs first |
| Event-free survival (EFS) in Part 1 and Part 2 participants only | Through end of study and up to approximately 2 years | 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 |
| Recurrence-free survival (RFS) in Part 1 and Part 2 participants only | Through end of study and up to approximately 2 years | 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 |
| Rate of cystectomy in all parts | Through end of study and up to approximately 2 years | Rate of cystectomy is defined as the proportion of participants who had a cystectomy while on study |
| Number of participants with adverse events (AEs) in Part 3 participants only | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | AEs as characterized by type, frequency, severity (CTCAE v5.0), seriousness, and relatedness to study drug(s) |
| Number of participants with laboratory abnormalities in Part3 participants only | From the first day through 30-37 days after the last study treatment, up to approximately 2 years | Laboratory abnormalities as characterized by type, frequency, severity |
Countries
France, Israel, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed