The study is designed to understand the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of MGC026 in participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors The study has a dose escalation portion and a cohort expansion portion of the study.

Participants will receive MGC026 by intravenous (IV) infusion. The dose of MGC026 will be assigned at the time of enrollment. Participants may receive up to 35 treatments if there are no severe side effects and as long as the cancer does not get worse. Participants will be monitored for side effects, and progression of cancer, have blood samples collected for routing laboratory work, and blood samples collected for research purposes.

Inclusion Criteria:

• Adults ≥ 18 years old, able to provide informed consent
• Adequate performance and laboratory parameters
• Availability of archival or formalin-fixed paraffin-embedded tumor tissue sample. Participants may undergo a fresh tumor biopsy to obtain a specimen for testing if an archival tumor sample is not available. Participants with no available archival tissue sample who cannot safely undergo a fresh biopsy as determined by consultation between the sponsor and investigator are eligible
• Unresectable, locally advanced or metastatic solid tumors including: squamous cell cancer (SCC) of the head and neck, esophageal SCC, squamous and non-squamous non-small cell lung cancer, small cell lung cancer, bladder cancer, sarcoma, endometrial cancer, melanoma, castration resistant prostate cancer, breast cancer, ovarian cancer, cervical cancer, colorectal cancer gastric or gastroesophageal cancer, pancreatic carcinoma, clear cell renal cell cancer or hepatocellular cancer.
• Measurable disease per RECIST v1.1. Participants with metastatic CRPC without measurable disease are eligible.
• Must be willing to use highly effective methods of birth control from the time of consent through 7 months after discontinuation of MGC026.
• Not pregnant or breastfeeding.

Exclusion Criteria:

• Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
• Another cancer that required treatment within the past 2 years, with the exception of those with low risk of cancer spreading or death such as adequately treated non melanomatous skin cancer, localized prostate cancer (Gleason Score < 6), or carcinoma in situ.
• Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on magnetic resonance imaging, computed tomography or positron emission tomography, or history of leptomeningeal disease or cord compression at the time of enrollment.
• Treatment with surgery, systemic cancer therapy, immunotherapy, chimeric antigen receptor-T therapy, or anti-hormonal within protocol specified intervals.
• Prior treatment with any B7-H3 targeted agent for cancer or any ADC with a topoisomerase payload.
• Prior autologous or allogeneic stem cell or solid organ transplant.
• Clinically significant cardiovascular, pulmonary, or gastrointestinal disorders.
• Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 1 week of first study drug administration.
• Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction.
• Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
• History of primary immunodeficiency.
• Major trauma or major surgery within 4 weeks of first study drug administration.
• Known hypersensitivity to recombinant proteins.