Clinical Trial 23901

• Overview

  Study Title:

  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

  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.

  Objective:

  Part 1 Primary Objectives: * To assess safety and tolerability at increasing dose levels of PF- 08052667 in participants with high-risk NMIBC in order to select the recommended monotherapy dose for further study and estimate the MTD (if reached). Part 2 Primary Objectives: * To assess safety and tolerability at increasing dose levels of PF- 08052667 in combination with BCG and/or sasanlimab in participants with high-risk NMIBC in order to select the RDEC/schedule and estimate the MTDC (if reached). Part 3 Primary Objectives: * To evaluate the anti-tumor efficacy of PF-08052667 in monotherapy and in combination with BCG and/or sasanlimab in participants with high-risk NMIBC Part 1 Secondary Objectives: * To characterize the single and multiple dose plasma and urine PK of PF-08052667 as monotherapy * To evaluate the immunogenicity of PF-08052667 * To evaluate preliminary antitumor activity of PF-08052667 as monotherapy * To evaluate the PD effect of PF- 08052667 on tumor associated immune cells in paired tumor/bladder biopsies Part 2 Secondary Objectives: * To characterize the single and multiple dose PK of PF-08052667 in combination with BCG and/or sasanlimab * To evaluate the immunogenicity of PF-08052667 in combination with BCG and/or sasanlimab * To evaluate preliminary antitumor activity of PF-08052667 in combination with BCG and/or sasanlimab * To evaluate the PK of sasanlimab administered in combination with PF-08052667 * To evaluate the immunogenicity of sasanlimab administered in combination with PF-08052667 * evaluate the PD effect of PF- 08052667 on tumor associated immune cells in paired tumor/bladder biopsies Part 3 Secondary Objectives: * To further assess the safety and tolerability of PF-08052667 as a monotherapy agent and in combination with BCG and/or sasanlimab at the RDEc in participants with high-risk NMIBC * To further evaluate the single and multiple dose PK of PF-08052667 * To evaluate the immunogenicity of PF-08052667 * To assess additional measures of anti-tumor efficacy of PF-08052667 in monotherapy and in combination with BCG and/or sasanlimab in participants with high-risk NMIBC * To evaluate the PK of sasanlimab administered in combination with PF-08052667 * To evaluate the immunogenicity of sasanlimab administered in combination with PF-08052667 * To evaluate PD effects of PF- 08052667 on tumor-associated immune cells in paired tumor/bladder biopsies

• Treatments

  Therapies:

  Antibody-Drug Conjugate; Immunotherapy; Therapy (NOS)

  Medications:

  BCG (); PF-02921367 (); PF-06801591 (Sasanlimab); PF-08052667 (); Sasanlimab ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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

• Exclusion Criteria

  Key Exclusion Criteria:
  • 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.

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