A Study of DES-1357 in People With Deficient Mismatch Repair (dMMR)/Microsatellite Instability-High (MSI-H) Metastatic Colorectal Cancer (mCRC)

This study is conducted sequentially in 3 parts. The primary objective for Part 1 is to determine the maximum tolerated dose of DES-1357 in participants with confirmed dMMR/MSI-H colorectal cancer (CRC). The primary objective for Part 2 is to assess the chronic tolerability and to identify the recommended Phase 2 dose (RP2D), to evaluate preliminary antitumor activity of the selected dose level of DES-1357, and to assess the pharmacokinetics (PK) and pharmacodynamics of DES-1357. The primary objective for Part 3 is to evaluate antitumor activity of the selected dose level of DES-1357.

Inclusion Criteria: Individuals must meet all of the following criteria to be included in the study: 1. Have read, understood, and signed the Informed Consent Form (ICF). 2. Male or female aged greater than or equal to (\>=) 18 years at the time of signing the ICF. 3. Histologically or cytologically confirmed carcinoma of the colon and/or rectum deemed unresectable and/or with evidence of metastases, that has been cytologically or genetically confirmed as dMMR, and/or MSI-H. 4. Demonstrated disease progression and/or intolerability to prior treatment with any of the following: pembrolizumab, nivolumab (±ipilimumab), dostarlimab, chemotherapy (ie, FOLFOX, FOLFIRI, CAPEOX, or FOLFOXIRI \[±bevacizumab\]), encorafenib/cetuximab, trastuzumab-based combinations, KRAS inhibitor/EGFR inhibitor, regorafenib, or TAS-102 (±bevacizumab) 5. Measurable disease according to RECIST version 1.1. 6. Adequate organ function: 1. Absolute neutrophil count \>=1,500 cells per/μL 2. Platelets \>=100,000 cells/μL 3. Hemoglobin \>=9 grams per deciliter (g/dL) 4. Total bilirubin less than or equal to (\) 470 milliseconds (msec) based on triplicate 12-lead ECGs obtained at screening. 7. Has an active infection. 8. Has known Human Immunodeficiency Virus (HIV) infection that is not under control. All of these criteria are required: undetectable viral RNA, CD4+ counts/levels \>=350, no history of Acquired Immune Deficiency Syndrome (AIDS)-defining opportunistic infection within the past 12 months, and clinically stable for at least 3 months on the same anti-HIV medications. 9. Has active or uncontrolled hepatitis B or C infection. Participants are eligible if they: 1. Have been curatively treated for hepatitis C virus infection as demonstrated clinically and by viral serologies 2. For hepatitis B, if the participant has a positive hepatitis B surface antigen result, viral load must be below 2000 international units per milliliter (IU/mL) in the absence of antiviral therapy for the last 12 weeks, and AST/ALT \