The purpose of the study is to explore the safety and effects of the study drug (PF-08046876) in people diagnosed with advanced cancer of the bladder, lung, head and neck, esophagus, or pancreas. PF-08046876 is an investigational anticancer therapy called an 'antibody drug conjugate' or 'ADC'. ADCs are anticancer drugs designed to stick to cancer cells and kill them.

The study drug will be given to participants through a needle in a vein (intravenous infusion). This study includes multiple parts. In the first part of the study, there will be different groups of people receiving different doses of the study drug. The study may also test different schedules.

Inclusion Criteria:

• 18 years of age or older
• Advanced cancer of the bladder, lung, head and neck, esophagus, or pancreas
• Measurable disease
• ECOG Performance status 0-1
• Part 1: progression or relapse following standard treatments
• Part 2: maximum of 2 prior lines of systemic therapy in the advanced setting
• Resolution of acute effects of prior anticancer therapy to baseline or Grade 1
• Consent to submit required pre-treatment tumor tissue as medically feasible

Exclusion criteria:

• Received prior treatment with an antibody drug conjugate with a camptothecin-class payload (e.g. sacituzumab govitecan, trastuzumab deruxtecan )
• Active anorexia, nausea or vomiting, and/or signs of intestinal obstruction meeting protocol exclusion
• Pulmonary disease meeting protocol exclusion
• Other unacceptable abnormalities as defined by protocol

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.