The purpose of the study is to explore the safety and effects of the study drug (PF-08046876) in people diagnosed with advanced cancer of the bladder, lung, head and neck, esophagus, or pancreas. PF-08046876 is an investigational anticancer therapy called an 'antibody drug conjugate' or 'ADC'. ADCs are anticancer drugs designed to stick to cancer cells and kill them. The study drug will be given to participants through a needle in a vein (intravenous infusion). This study includes multiple parts. In the first part of the study, there will be different groups of people receiving different doses of the study drug. The study may also test different schedules.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
310
Intravenous administration
Brigham and Women's Hospital
Boston, Massachusetts, United States
NOT_YET_RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
NOT_YET_RECRUITINGDana-Farber Cancer Institute - Chestnut Hill
Newton, Massachusetts, United States
NOT_YET_RECRUITINGSarah Cannon Research Institute - Pharmacy
Nashville, Tennessee, United States
NOT_YET_RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
NOT_YET_RECRUITINGThe University of Texas MD Anderson Cancer Center - Conroe
Conroe, Texas, United States
NOT_YET_RECRUITINGUniversity of Texas MD Anderson Cancer Center
Houston, Texas, United States
NOT_YET_RECRUITINGThe University of Texas, MD Anderson Cancer Center - West Houston
Houston, Texas, United States
NOT_YET_RECRUITINGThe University of Texas, MD Anderson Cancer Center - League City
League City, Texas, United States
NOT_YET_RECRUITINGNEXT Oncology
San Antonio, Texas, United States
RECRUITING...and 3 more locations
Incidence of Treatment Emergent Adverse Events (TEAEs) estimated during the Adverse Events (AE) evaluation
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy dose modifications.
Time frame: Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first)
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy
Occurrence of DLTs as defined by the protocol
Time frame: Baseline to end of DLT evaluation period
Part 1: Recommended Monotherapy Dose for Expansion
RDE will be based on cumulative safety, preliminary antitumor activity and pharmacokinetics findings
Time frame: Baseline to 30 days post last study drug administration
Part 2: Recommended Phase 2 Dose
RP2D will be determined based on the cumulative safety, preliminary anti tumor activity and Pharmacokinetics findings.
Time frame: Baseline to 30 days post last study drug administration
Objective Response Rate (ORR)
ORR defined as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Time frame: Baseline until the date of the first documentation of disease progression, death, or start of new anticancer therapy (approximately 2 years)
Duration of Response (DOR)
DOR as defined per RECIST 1.1.
Time frame: From the date of the first objective response to the date of disease progression or death (approximately 2 years)
Progression Free Survival (PFS)
PFS as defined per RECIST 1.1.
Time frame: From Baseline to date of first disease progression or death (approximately 2 Years)
Overall Survival (OS)
OS defined as the time until death due to any cause.
Time frame: From baseline to up to 3 years
Pharmacokinetics (PK): Maximum Observed Serum Concentration (Cmax)
Evaluate the single and multiple dose PK of PF-08048676.
Time frame: Baseline to approximately 30 days after last dose of study drug
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Evaluate the single and multiple dose PK of PF-08048676.
Time frame: Baseline to approximately 30 days after last dose of study drug
PK: Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast)
Evaluate the single and multiple dose PK of PF-08048676.
Time frame: Baseline to approximately 30 days after last dose of study drug
Incidence of Anti-Drug Antibody (ADA)
To evaluate the immunogenicity of PF-08046876.
Time frame: Baseline to approximately 30 days after last dose of study drug
Incidence of Neutralizing Antibodies (NAb)
To evaluate the immunogenicity of PF-08046876.
Time frame: Baseline to approximately 30 days after last dose of study drug
Percent change of immune cells within tumors based on multiplex immunofluorescence
This measure will assess changes in the presence or activation of immune cells in the tumor microenvironment using RNA and/or Immunohistochemistry (IHC) assays.
Time frame: Baseline through 4-7 weeks after first dose of study drug
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