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

Open to people ages 18 years and up

• 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

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.

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