RecruitingInterventionalPhase 1

A Phase 1 Study to Investigate PF-08046033 in Participants With Advanced Solid Tumors

NCT ID: NCT07519655Sponsor: PfizerLast updated: 2026-04-23

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.

Arms & interventions

DrugPF-08046033
Powder for solution for infusion.

Outcome measures

Primary

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

Secondary

Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by investigator
Time frame: Up to 3 years
Duration of response (DOR) using RECIST v1.1 as assessed by investigator
Time frame: Up to 3 years
Progression-free survival (PFS) using RECIST v1.1 as assessed by investigator
Time frame: Up to 3 years
Overall survival (OS) using RECIST v1.1 as assessed by investigator
Time frame: Up to 3 years
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) 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
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
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
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)
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
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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.

Study locations (4)

Presbyterian/St Lukes Medical Center

Denver, Colorado, 80218

Recruiting

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218

Recruiting

Sarah Cannon Research Institute- Pharmacy

Nashville, Tennessee, 37203

Not Yet Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Not Yet Recruiting