Inclusion Criteria:  Histologic or cytologic evidence of malignant solid tumor with advanced disease (except primary central nervous system [CNS] neoplasms), defined as cancer that is either metastatic or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered to result in reasonable clinical benefit). Disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the Investigator's judgment likely to result in clinical benefit, or if such therapy has been refused by the subject. Documentation of the reason must be provided for subjects who have not received a standard therapy likely to result in clinical benefit. Eastern Cooperative Oncology Group Performance Status score of 0 or 1. Adequate baseline hematologic and organ function. Willing to use contraception.  Additional Inclusion for Part 2: Histologic or cytologic evidence of malignancy (melanoma/uveal melanoma, colorectal cancer, prostate cancer, mesothelioma).  Exclusion Criteria:  Subjects who have participated in Part 1 dose escalation are not eligible to enroll in Part 2 dose expansion. Persistent clinically significant toxicities from previous anticancer therapy (excluding alopecia). Treatment with cytotoxic, biologic, or targeted therapies for advanced cancer within 14 days before administration of the subject's first dose of KZR-261. Treatment with an investigational drug within 28 days before administration of the subject's first dose of KZR-261. Radiation therapy within 14 days of before administration of the subject's first dose of KZR-261. Major surgical procedure within 28 days before administration of the subject's first dose of KZR-261. History of risk factors for Torsades de pointes. Active, symptomatic CNS metastases or primary CNS malignancy. Any female who is breastfeeding or who plans to become pregnant during the study, or who are actively trying to conceive at the time of signing of the informed consent form (ICF). Uncontrolled, clinically significant pulmonary disease.