Overview

This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat.

Patients in this study must have cancer that has come back or did not get better with treatment. Patients must have a solid tumor cancer that can't be treated with standard of care drugs.

This clinical trial uses an experimental drug called PF-08052666/SGN-MesoC2. PF-08052666/SGN-MesoC2 is a type of antibody-drug conjugate (ADC). ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells.

This study will have 3 parts. Part A and Part B of the study will find out how much PF-08052666/SGN-MesoC2 should be given to participants. Part C will use the information from Parts A and B to see if PF-08052666/SGN-MesoC2 is safe and if it works to treat solid tumor cancers.

Eligibility

Inclusion Criteria:

• Aged 18 years or older.
• Histologically- or cytologically-confirmed metastatic or locally advanced unresectable platinum-resistant ovarian cancer, NSCLC, pancreatic ductal adenocarcinoma, endometrial cancer, colorectal cancer, or mesothelioma, who have relapsed or progressed following standard therapies, or for which no standard therapies are available.
• An Eastern Cooperative Oncology Group performance status score of 0 or 1.
• At least 1 measurable lesion at baseline based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
• Archival tumor tissue or a fresh tumor biopsy during the screening period.
• Adequate hepatic, renal and bone marrow function.
• Participants must not have received more than 2 lines of cytotoxic systemic therapy in the metastatic setting (Parts B and C only).

Exclusion Criteria:

• Previously received or currently receiving any systemic anticancer therapy or focal radiotherapy within 4 weeks prior to the first dose of MesoC2 or within 2 weeks prior to the first dose of MesoC2 if the underlying disease had progressed on treatment.
• Prior anti-MSLN antibody or MSLN-directed ADC (Part C only).
• Unresolved toxicities from prior therapy greater than NCI CTCAE v5.0 grade 1 at the time of study treatment (except alopecia).
• Inadequate hepatic dysfunction, renal function, or hematologic abnormalities.
• Previously untreated brain metastases. Participants who received radiation or surgery for brain metastases are eligible if therapy was completed at least 4 weeks prior to study treatment initiation, and there was no evidence of central nervous system progression nor requirements for chronic corticosteroid therapy