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

Phase 1

Not yet recruiting

• Conditions: Malignant Melanoma; Melanoma; Metastatic Melanoma; Solid Tumors
• Interventions: Drug: PF-08046031

• Registration Number: NCT06799533
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-23
• Study First Submitted QC: 2025-01-23
• Study First Posted: 2025-01-29
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-16
• Study Start: 2025-04-18
• Primary Completion: 2029-05-10
• Study Completion: 2030-05-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 185

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.
  • 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

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

Other protocol specific criteria might apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PF-08046031 monotherapy	PF-08046031	PF-08046031

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events (AEs)	through 30 days after the last study treatment; approximately 6 months	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.
Number of participants with laboratory abnormalities	through 30days after the last study treatment; approximately 6 months
Number of participants with dose limiting toxicities	up to 28 days

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) parameter - Area under the curve (AUC)	Through 30 days after the last study treatment; approximately 6 months	To be summarized using descriptive statistics
PK parameter - Maximum Concentration (Cmax)	Through 30 days after the last study treatment; approximately 6 months	To be summarized using descriptive statistics
PK parameter - Time to maximum concentration (Tmax)	Through 30 days after the last study treatment; approximately 6 months	To be summarized using descriptive statistics
PK parameter - Apparent terminal half-life (t1/2)	Through 30 days after the last study treatment; approximately 6 months	To be summarized using descriptive statistics
PK parameter - Trough concentration (Ctrough)	Through 30 days after the last study treatment; approximately 6 months	To be summarized using descriptive statistics
number of participants with antidrug antibodies	through 30 days after the last study treatment; approximately 6 months	To be summarized using descriptive statistics
Objective response rate (ORR)	Up to approximately 1 year	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 investigator
Duration of response (DOR)	Up to approximately 1 year	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
Progression-free survival (PFS)	Up to approximately 1 year	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
Overall survival (OS)	Approximately 2 years	The time from the start of study treatment to death due to any cause