The purpose of this first-in-human study, CTMX-2051-101, is to characterize the safety, tolerability, and antitumor activity of CX-2051 as a monotherapy and in combination with bevacizumab in adult participants with advanced solid tumors.

The study is comprised of 2 parts. Part 1 involves CX-2051 dose escalation to identify the maximum tolerated dose (MTD) of CX-2051 as monotherapy and as combination therapy (CX-2051 combined with bevacizumab). Part 2 (dose expansion) will further assess safety and tolerability as well as preliminarily assess antitumor activity of CX-2051 as monotherapy and/or combination therapy in indication-specific expansion cohorts.

Inclusion Criteria:

• Metastatic or locally advanced unresectable solid tumor that has progressed after standard therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Measurable disease per RECIST v1.1
• Consent to fresh biopsy or if medically contraindicated, recent (within 6 months) archival tumor tissue
• Additional inclusion criteria may apply

Exclusion Criteria:

• Recent history (within last 2 years) of localized cancers that are not related to the current cancer being treated
• Known active central nervous system (CNS) involvement by malignancy
• Systemic anticancer treatment, radiotherapy, or investigational agent(s) within 14 days prior to C1D1
• Previous treatment with antibody-drug conjugates (ADCs) with Topo-I inhibitor payload
• Major surgery (requiring general anesthesia) within 4 weeks prior to C1D1
• Elevated baseline laboratory values
• Serious concurrent illness
• Pregnant or breast feeding
• Additional exclusion criteria may apply