This is an early-stage (Phase 1) clinical study testing a new study medicine called PF-08046033. The goal of the study is to understand how safe the medicine is, how well people tolerate it, how it behaves in the body, and whether it shows early signs of helping to treat cancer. The study includes adult participants who have advanced cancers that cannot be removed by surgery or have spread to other parts of the body. These cancers include non-small cell lung cancer, esophageal squamous cell cancer, and melanoma. The study has two parts: In the first part, small groups of participants receive increasing doses of the study medicine. This helps researchers find a dose that is safe and suitable for further testing. Once a suitable dose is identified, the second part enrolls more participants with specific cancer types to better understand the safety of the medicine and whether it shows signs of helping control the cancer. Participants receive the study medicine through regular treatment cycles and are closely monitored for side effects and how their cancer responds. The information from this study will help researchers decide whether PF-08046033 should be studied further in later-stage clinical trials.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
250
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Presbyterian/St Lukes Medical Center
Denver, Colorado, United States
RECRUITINGSarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
RECRUITINGSmilow Cancer Hospital - Yale New Haven Health
New Haven, Connecticut, United States
RECRUITINGYale - New Haven Hospital - Yale Cancer Center
New Haven, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut, United States
RECRUITINGYale University - Smilow Cancer Hospital; C/O Thomas Ferencz, RPh, BCOP
New Haven, Connecticut, United States
RECRUITINGSmilow Cancer Hospital - Trumbull
Trumbull, Connecticut, United States
RECRUITINGSarah Cannon Research Institute- Pharmacy
Nashville, Tennessee, United States
RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
RECRUITINGInova Schar Cancer Infusion Pharmacy
Fairfax, Virginia, United States
RECRUITING...and 5 more locations
Type, incidence and severity of participants with adverse events (AEs)
Type, incidence, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v 5.0), seriousness, and relatedness of adverse events (AEs).
Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 1 year
Type, incidence, and severity of participants with laboratory abnormalities
Type, incidence, and severity (graded by NCI CTCAE version 5.0) of laboratory abnormalities
Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 1 year
Number of participants with dose modifications
Frequency of dose modifications (eg, dose delay and treatment discontinuations) due to AEs
Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 1 year
Incidence of dose-limiting toxicities (DLTs)
To identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) of PF-08046033
Time frame: From the first day through 30-37 days after the last study treatment, up to approximately 1 year
Recommended dose and schedule of PF-08046033 for expansion (RDE)
RDE will be based on cumulative safety, preliminary antitumor activity and pharmacokinetics findings
Time frame: Up to 1 year
Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by investigator
Objective response defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, from the date of first dose until the date of the first documentation of PD, death, or start of new anticancer therapy, whichever occurs first.
Time frame: Up to 3 years
Duration of response (DOR) using RECIST v1.1 as assessed by investigator
DOR is defined as the time from first documentation of CR or PR to date of first documentation of PD or death due to any cause.
Time frame: Up to 3 years
Progression-free survival (PFS) using RECIST v1.1 as assessed by investigator
Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective progressive disease (PD) assessed by investigator per RECIST 1.1, or death due to any cause, whichever occurs first.
Time frame: Up to 3 years
Overall survival (OS) using RECIST v1.1 as assessed by investigator
Overall survival defined as the time from the date of randomization to the date of death due to any cause.
Time frame: Up to 3 years
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of PF-08046033
To characterize the PK of PF-08046033
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, , Up to approximately 1 year
PK: Area under the concentration-time curve (AUC) of PF-08046033
To characterize the PK of PF-08046033
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year
PK: Time to Maximum concentration (Tmax) of PF-08046033
To characterize the PK of PF-08046033
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year
PK: Trough concentration (Ctrough) of PF-08046033
To characterize the PK of PF-08046033
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year
PK: Terminal Elimination half-life (t1/2) of PF-08046033
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year
Incidence of antidrug antibodies (ADAs)
To characterize the immunogenicity of PF-08046033
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year
Percent change of immune cells and PD-L1 expression based on immunohistochemistry
To evaluate the pharmacodynamic effects of PF-08046033 in tumor tissue
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year
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