Urothelial Cancer, Advanced/Metastatic Urothelial Cancer, Urothelial Carcinoma
Conditions
Keywords
urothelial cancer, metastatic urothelial cancer, locally advanced urothelial cancer, bladder cancer, urothelial carcinoma, PD-1, VEGF
Brief summary
This study is being done to learn more about a new medicine called PF-08634404. It is for adults with a type of bladder cancer called locally advanced or metastatic urothelial cancer (LA/mUC), meaning the cancer has spread to nearby tissues or other parts of the body. The purpose of the study is to see if PF-08634404 is safe, how well it works, how it moves through the body, and how it affects the cancer. The study will also look at how the medicine may change certain markers in the body that are linked to cancer. To join the study, participants must: * Be adults (18 years or older) and * Have locally advanced or metastatic urothelial cancer, The study has two groups: * Cohort A: People who have already received treatment for their cancer will get the study medicine ( PF-08634404) alone. * Cohort B: People who have not had treatment before will get the study medicine along with another cancer medicine called enfortumab vedotin. Everyone in the study will get the study medicine through a vein (IV infusion) with or without enfortumab vedotin. Treatment will continue as long as it helps and side effects are manageable. Before starting, participants will go through a screening period to check if they are eligible. During the study, they will have regular visits for treatment, health checks, and tests to see how the cancer is responding. Scans will be done regularly to monitor the cancer. If the cancer gets worse but the treatment is still helping and side effects are manageable, participants may be allowed to continue treatment with their doctor's and the sponsor's agreement.
Interventions
BIOLOGICALPF-08634404
Concentrate for solution for Infusion.
BIOLOGICALEnfortumab Vedotin
Powder for concentrate for solution for infusion
Sponsors
Pfizer
Astellas Pharma Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at the time of screening. * Histologically confirmed locally advanced or metastatic urothelial carcinoma (LA/mUC). * Measurable disease per RECIST v1.1 criteria. * ECOG performance status of 0 or 1. * Adequate organ function, including hematologic, hepatic, and renal parameters. * Willingness to comply with study procedures and provide informed consent. * For participants of childbearing potential: agreement to use effective contraception during the study and for a defined period after the last dose.
Exclusion criteria
Participants will be excluded if they meet any of the following: * History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy * Known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression * Active autoimmune diseases requiring systemic treatment within the past 2 years * Participation in another investigational study within 30 days or 5 half-lives of the investigational product. * Pregnant or breastfeeding individuals. * Inability or unwillingness to comply with study requirements. * Study staff or their immediate family members directly involved in the conduct of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Objective Response Rate (ORR) by investigator | Up to approximately 3 years | ORR is defined as the proportion of participants in the analysis population having a BOR of confirmed CR or confirmed PR according to RECIST v1.1 as assessed by investigator. |
| Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Through 90 days after the last study intervention; Up to approximately 3 years | AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study intervention. |
| Number of participants with dose limiting toxicity (DLT) in Part 1 of Cohort B | Through 90 days after the last study intervention; Up to approximately 3 years | The number of participants who experienced DLTs in participants receiving PF-08634404 in combination with EV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) per RECIST v1.1 by investigator | Up to approximately 3 years | DOR is defined as the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. |
| Progression Free Survival (PFS) per RECIST v1.1 by investigator | Up to approximately 3 years | Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by investigator per RECIST v1.1, or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to approximately 3 years | Overall survival defined as the time from the date of C1D1 to the date of death due to any cause. |
| Number of Participants With Clinical Laboratory Abnormalities | Through 90 days after the last study intervention; Up to approximately 3 years | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) |
| Pharmacokinetics (PK): Serum concentration of PF-08634404 | Up to 37 days after the last dose of treatment | To characterize the pharmacokinetics (PK) of PF-08634404 as monotherapy in participants with previously treated LA/mUC and in combination with EV in participants with previously untreated LA/mUC. |
| Incidence of Anti-Drug Antibody (ADA) against PF-08634404 | Up to 37 days after the last dose of treatment | To evaluate the immunogenicity of PF-08634404 as monotherapy in participants with previously treated LA/mUC and in combination with EV in participants with previously untreated LA/mUC. |
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed