The trial was terminated for strategic reasons. The decision was not based on any safety concerns.

This study will test the safety of a drug called PF-08046049/SGN-BB228 in participants with melanoma and other solid tumors that are hard to treat 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.

This study will have 3 parts. Parts A and B of the study will find out how much PF-08046049/SGN-BB228 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046049/SGN-BB228 is safe and if it works to treat solid tumor cancers.

Inclusion Criteria:

• All Parts: Participants must have disease that is relapsed, refractory, or intolerant to standard of care. Participants must have histologically or cytologically confirmed metastatic malignancy.

• Participants must have one of the following tumor types:

  • Parts A and B: Participants must have metastatic or unresectable cutaneous melanoma.

  • Part C: Participants must have one of the following tumor types:

    • Cutaneous Melanoma
    • Non-small Cell Lung Cancer (NSCLC)
    • Colorectal Cancer (CRC)
    • Pancreatic Cancer
    • Mesothelioma

• A pre-treatment biopsy or submission of archival tissue is required

• For participants with cutaneous melanoma

  • Must have been previously treated with an anti-programmed death-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) agent given alone or with other therapies.
  • Participants with a targetable BRAF mutation must have been treated with, been intolerant of, or been deemed ineligible to receive treatment with BRAF/MEK targeted therapy prior to study entry.

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

• Measurable disease per RECIST v1.1 at baseline

Exclusion Criteria:

• History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.

• Active central nervous system metastases or leptomeningeal disease. Participants with previously treated brain metastases may participate provided they are:

  • clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment,
  • they have no new or enlarging brain metastases,
  • and are off of corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study drug.

• Prior therapies cannot include any drugs targeting CD228 or 4-1BB

• Immunotherapy, biologics, and/or other approved or investigational antitumor treatment that is not completed 4 weeks prior to first dose of study drug, or within 2 weeks prior to the first dose of study drug if the underlying disease has progressed on treatment

• Melanoma subtypes including acral, uveal, and mucosal are excluded

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.