Cutaneous Melanoma, Esophageal Cancer, Non-Small-Cell Lung
Conditions
Keywords
Lung cancer, Esophageal cancer, Melanoma, Antibody drug conjugate
Brief summary
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.
Interventions
DRUGPF-08046033
Powder for solution for infusion.
Sponsors
Pfizer
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
1. Participants must have histologically-confirmed metastatic or unresectable locally advanced NSCLC, ESCC, or cutaneous melanoma. 2. Participants must have disease that has progressed on or be unable to tolerate standard treatments (Part 1) or 1-2 prior systemic therapies (Part 2). 3. Participants must have measurable disease. 4. Eastern Cooperative Oncology Group (ECOG) performance status is 0-1.
Exclusion criteria
1. Participants with known clinically active central nervous system (CNS) metastases. 2. Participants with pre-existing neuropathy ≥Grade 2 per NCI CTCAE v 5.0. 3. Uncontrolled diabetes mellitus with hemoglobin (Hgb) A1C ≥10.0%. 4. Untreated clinically significant thromboembolic disease. 5. Previous exposure to GPNMB-targeted therapy. 6. Known or suspected hypersensitivity to any component or excipient contained in the drug formulation of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type, incidence and severity of participants with adverse events (AEs) | From the first day through 30-37 days after the last study treatment, up to approximately 1 year | 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). |
| Type, incidence, and severity of participants with laboratory abnormalities | From the first day through 30-37 days after the last study treatment, up to approximately 1 year | Type, incidence, and severity (graded by NCI CTCAE version 5.0) of laboratory abnormalities |
| Number of participants with dose modifications | From the first day through 30-37 days after the last study treatment, up to approximately 1 year | Frequency of dose modifications (eg, dose delay and treatment discontinuations) due to AEs |
| Incidence of dose-limiting toxicities (DLTs) | From the first day through 30-37 days after the last study treatment, up to approximately 1 year | To identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) of PF-08046033 |
| Recommended dose and schedule of PF-08046033 for expansion (RDE) | Up to 1 year | RDE will be based on cumulative safety, preliminary antitumor activity and pharmacokinetics findings |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by investigator | Up to 3 years | 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. |
| Duration of response (DOR) using RECIST v1.1 as assessed by investigator | Up to 3 years | 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. |
| Progression-free survival (PFS) using RECIST v1.1 as assessed by investigator | Up to 3 years | 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. |
| Overall survival (OS) using RECIST v1.1 as assessed by investigator | Up to 3 years | Overall survival defined as the time from the date of randomization to the date of death due to any cause. |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of PF-08046033 | From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, , Up to approximately 1 year | To characterize the PK of PF-08046033 |
| PK: Area under the concentration-time curve (AUC) of PF-08046033 | From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year | To characterize the PK of PF-08046033 |
| PK: Time to Maximum concentration (Tmax) of PF-08046033 | From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year | To characterize the PK of PF-08046033 |
| PK: Trough concentration (Ctrough) of PF-08046033 | From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year | To characterize the PK of PF-08046033 |
| PK: Terminal Elimination half-life (t1/2) of PF-08046033 | From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year | — |
| Incidence of antidrug antibodies (ADAs) | From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year | To characterize the immunogenicity of PF-08046033 |
| Percent change of immune cells and PD-L1 expression based on immunohistochemistry | From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year | To evaluate the pharmacodynamic effects of PF-08046033 in tumor tissue |
Countries
Puerto Rico, South Korea, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed