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

Официальное название

A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTITUMOR ACTIVITY OF PF-08052667 AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 18 YEARS OF AGE AND OLDER WITH BLADDER CANCER

Обзор

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.

Вмешательства

• Препарат PF-08052667
  PF-08052667 will be administered intravesical (IVe) instillation following a PF-02921367 (DDM) bladder pre-wash
• Препарат Sasanlimab
  Sasanlimab will be administered as subcutaneous (SC) injection
• Препарат BCG
  BCG will be administered intravesical (IVe) instillation
• Препарат PF-02921367
  PF-02921367 (DDM) is a 10-min pre- wash and will be administered intravesical (IVe) instillation

Первичные конечные точки

• Number of participants with dose limiting toxicities (DLTs) in dose escalation in Part 1 and Part 2 participants only [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Through end of study and up to approximately 2 years]
• Event-free survival (EFS) in Part 3 participants only [Срок оценки: Through end of study and up to approximately 2 years]

Вторичные конечные точки (12)

• PK: Maximum Observed Serum Concentration (Cmax) [Срок оценки: From the first day through 30-37 days after the last study treatment]
• PK: Time to Reach Maximum Observed Serum Concentration (Tmax) [Срок оценки: From the first day through 30-37 days after the last study treatment]
• PK: Minimum observed serum concentration (Ctrough) [Срок оценки: 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) [Срок оценки: From the first day through 30-37 days after the last study treatment]
• PK: Half-life (t1/2) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: Through end of study and up to approximately 2 years]
• Complete Response Rate (CRR) in Part 1 and Part 2 participants only [Срок оценки: Through end of study and up to approximately 2 years]
• Overall survival (OS) in Part 3 participants only [Срок оценки: Through end of study approximately 5 years from last participant enrollment]
• Cystectomy-free survival in all Parts [Срок оценки: Through end of study and up to approximately 2 years]
• Event-free survival (EFS) in Part 1 and Part 2 participants only [Срок оценки: Through end of study and up to approximately 2 years]
• Recurrence-free survival (RFS) in Part 1 and Part 2 participants only [Срок оценки: Through end of study and up to approximately 2 years]

Критерии участия

Критерии включения

• 18 years of age or older (or the minimum age of consent per local regulations)
• 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
• 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.
• Have refused or are ineligible or not appropriate for radical cystectomy
• 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
• ECOG PS 0 or 1

Критерии исключения

• Concomitant anti-cancer therapy for Non-Muscle Invasive Bladder Cancer (NMIBC); and prior radiation therapy to the bladder are not allowed
• Renal or hepatic impairment; and hematologic abnormalities as defined in the protocol
• Participants with active, uncontrolled infection as specified in the protocol

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 54 центра

• The Kirklin Clinic of UAB Hospital — Birmingham
• UAB Infusion Therapy Extended Care Clinic (ECC) — Birmingham
• The University of Alabama at Birmingham Investigation Drug Services Pharmacy — Birmingham
• University of Alabama at Birmingham — Birmingham
• Moffitt Cancer Center at SouthShore — Ruskin
• Moffitt Cancer Center - International Plaza — Tampa
• Moffitt Cancer Center - McKinley Campus — Tampa
• Moffitt Cancer Center — Tampa
• … и ещё 46 центров

Израиль · 4 центра

• Rabin Medical Center — Petah Tikva
• Sheba Medical Center — Ramat Gan
• Hadassah Medical Center — Jerusalem
• Rambam Health Care Campus — Haifa

Великобритания · 4 центра

• Sheffield Teaching Hospitals NHS Foundation Trust — Sheffield
• Royal Hallamshire Hospital — Sheffield
• The University of Sheffield — Sheffield
• Weston Park Cancer Centre — Sheffield

South Korea · 3 центра

• Samsung Medical Center — Seoul
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul

Франция · 2 центра

• Gustave Roussy — Villejuif
• Pitie Salpetriere University Hospital — Paris

Испания · 1 центр

• Hospital Universitario 12 de Octubre — Madrid

Публикации

• Carosino CM, Olson DJ, Mazahreh RC, Ortiz DJ, Duniho S, Moskovitz E, Gray M, Hein RF, Garcia NH, Ardalani H, Farr L, Yan T, Burcher M, Mikell I, Levengood MR, Sandall S, Dekker JD. An Integrin beta6-targeted antibody-drug conjugate optimized for intravesical delivery to treat non-muscle invasive bladder cancer. Mol Cancer Ther. 2026 Apr 20. doi: 10.1158/1535-7163.MCT-26-0077. Online ahead of print PMID 42008114

Идентификаторы

NCT: NCT07206225 · C6001001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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