Phase 1 Study of PF-08046033 in Advanced Solid Tumors

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

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 Overview

• Status: Recruiting
• Conditions: Esophageal Cancer; Cutaneous Melanoma; Non-Small-Cell Lung
• Intervention / Treatment: Drug: PF-08046033

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Pan American Center for Oncology Trials, LLC
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Hospital Oncologico Dr. Isaac Gonzalez-Martinez
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute at HealthONE
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Presbyterian/St Lukes Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • SCRI Oncology Partners
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • Sarah Cannon Research Institute- Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Cohort 1; Participants will receive PF-08046033 dose level 1 intravenously (IV).	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 1: Cohort 2; Participants will receive PF-08046033 dose level 2 IV.	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 1: Cohort 3; Participants will receive PF-08046033 dose level 3 IV.	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 1: Cohort 4; Participants will receive PF-08046033 dose level 4 IV.	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 1: Cohort 5; Participants will receive PF-08046033 dose level 5 IV.	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 1: Cohort 6; Participants will receive PF-08046033 dose level 6 IV.	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 1: Cohort 7; Participants will receive PF-08046033 dose level 7 IV.	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 2: Cohort 1 Non-Small Cell Lung Cancer (NSCLC); PF-08046033: Specified dose IV on specified days	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 2: Cohort 3 (Cutaneous Melanoma); PF-08046033: Specified dose IV on specified days	Drug: PF-08046033; Powder for solution for infusion.
Experimental: Part 2: Cohort 2 Esophageal Squamous Cell Carcinoma (ESCC); PF-08046033: Specified dose IV on specified days	Drug: PF-08046033; Powder for solution for infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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	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	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	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	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Up to 3 years
PK: Area under the concentration-time curve (AUC) of PF-08046033	To characterize the PK of PF-08046033	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	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	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		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	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	From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, Up to approximately 1 year
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of PF-08046033	To characterize the PK of PF-08046033	From Cycle 1 Day 1 (each cycle is 21 days) until End of Treatment, , Up to approximately 1 year

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2026
• Primary Completion (Estimated): July 14, 2028
• Study Completion (Estimated): July 14, 2029

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Lung cancer; Melanoma; Esophageal cancer; Antibody drug conjugate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Head and Neck Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Esophageal Diseases; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Lung Neoplasms; Esophageal Neoplasms; Melanoma
• Other Study ID Numbers: C5921001; GPS [GPNMB-AurS] (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No