A Study to Learn About the Study Medicine Called PF-08046031 in Advanced Melanoma and Other Solid Tumors

AN OPEN-LABEL PHASE 1 STUDY TO INVESTIGATE PF-08046031 IN ADULTS WITH ADVANCED MELANOMA AND OTHER SOLID TUMORS

This study will test the safety of a drug called PF-08046031 in participants with melanoma and other solid tumors that have no current approved treatment or have spread through the body. It will also study the side effects of this drug. A side effect is anything a drug does to the body besides treating the disease. The study will have 3 parts. Part A and B of the study will find out how much PF-08046031 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046031 is safe and if it works to treat solid tumor cancers.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Metastatic Melanoma; Solid Tumors; Malignant Melanoma
• Intervention / Treatment: Drug: PF-08046031

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Val-de-marne
    • Villejuif, Val-de-marne, France, 94800
      • Gustave Roussy
• Spain
  • Barcelona [barcelona]
    • Barcelona, Barcelona [barcelona], Spain, 08035
      • Hospital Universitari Vall d'Hebron
• Sweden
  • Stockholms LÄN [se-01]
    • Solna, Stockholms LÄN [se-01], Sweden, 171 64
      • Karolinska Universitetssjukhuset Solna
• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institue, A Cedars-Sinai Affiliate
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • San Francisco, California, United States, 94158
      • UCSF Medical Center, Investigational Pharmacy
    • Santa Monica, California, United States, 90404
      • The Angeles Clinic and Research Institue, A Cedars-Sinai Affiliate (Emergency Back-up only)
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE - SCRI - PPDS
    • Denver, Colorado, United States, 80218
      • Presbyterian/ St. Lukes Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants in Part 1 (dose escalation) must have histologically- or cytologically-confirmed metastatic or unresectable cutaneous melanoma. They must have progressive disease following at least 1 prior anti programmed death-1 (PD 1)/programmed death-ligand 1 (PD L1) immunotherapy containing regimen (either as monotherapy, or in combination with other checkpoint inhibitors or other therapies) and should have no appropriate standard therapy available at the time of enrollment in the judgment of the investigator.
• Participants in Part 2 (dose optimization) must have histologically- or cytologically-confirmed metastatic or unresectable cutaneous melanoma. They must have progressive disease following at least 1 prior anti PD 1/PD L1 immunotherapy containing regimen (either as monotherapy, or in combination with other checkpoint inhibitors or other therapies) but not more than 2 total prior lines of systemic therapy and should have no appropriate standard therapy available at the time of enrollment in the judgment of the investigator.
• For Part 3 (dose expansion): Participants must have histologically- or cytologically confirmed metastatic or unresectable solid malignancy from 1 of the following tumor types: cutaneous melanoma, NSCLC, HNSCC, esophageal cancer.

Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 Measurable disease per RECIST v1.1 at baseline

• Participants who have refused available standard of care therapies are not eligible.

Exclusion Criteria:

• Active cerebral/meningeal disease related to the underlying malignancy. Previous exposure to CD228-targeted therapy, vedotin or an MMAE-containing agent, or any taxane containing regimen for advanced disease.

Melanoma subtypes including uveal, and mucosal are excluded. Chemotherapy, definitive radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of study intervention, or within 2 weeks prior to first dose of study intervention if the underlying disease has progressed on treatment

• Grade 3 or higher pulmonary disease unrelated to underlying malignancy. Previous history of non-infectious interstitial lung disease (ILD) or pneumonitis that required steroids, current ILD or pneumonitis, or suspected ILD or pneumonitis that cannot be ruled out by imaging at screening.

Other protocol specific criteria might apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-08046031 monotherapy; PF-08046031	Drug: PF-08046031; Given into the vein (IV; intravenous)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose limiting toxicities		up to 28 days
Number of participants with adverse events (AEs)	Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	through 30 days after the last study treatment; approximately 6 months
Number of participants with laboratory abnormalities		through 30days after the last study treatment; approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	The time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of progressive disease (PD) (based on radiographic assessments per RECIST v1.1) or death due to any cause	Up to approximately 1 year
Progression-free survival (PFS)	The time from the start of study treatment to the first documentation of PD (per RECIST v1.1 as assessed by the investigator) or death due to any cause	Up to approximately 1 year
Overall survival (OS)	The time from the start of study treatment to death due to any cause	Approximately 2 years
number of participants with antidrug antibodies	To be summarized using descriptive statistics	through 30 days after the last study treatment; approximately 6 months
Pharmacokinetic (PK) parameter - Area under the curve (AUC)	To be summarized using descriptive statistics	Through 30 days after the last study treatment; approximately 6 months
PK parameter - Maximum Concentration (Cmax)	To be summarized using descriptive statistics	Through 30 days after the last study treatment; approximately 6 months
PK parameter - Time to maximum concentration (Tmax)	To be summarized using descriptive statistics	Through 30 days after the last study treatment; approximately 6 months
PK parameter - Apparent terminal half-life (t1/2)	To be summarized using descriptive statistics	Through 30 days after the last study treatment; approximately 6 months
PK parameter - Trough concentration (Ctrough)	To be summarized using descriptive statistics	Through 30 days after the last study treatment; approximately 6 months
Objective response rate (ORR)	The proportion of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigato	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): May 1, 2025
• Primary Completion (Actual): February 23, 2026
• Study Completion (Actual): February 23, 2026

Study Registration Dates

• First Submitted: January 23, 2025
• First Submitted That Met QC Criteria: January 23, 2025
• First Posted (Actual): January 29, 2025

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Solid tumors; Other Solid tumors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma
• Other Study ID Numbers: C5901001; 2024-514745-10-00 (Registry Identifier: CTIS (EU))

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
• product manufactured in and exported from the U.S.: Yes