The main inclusion criteria include but are not limited to the following: - Participant with MSS/MSI-L CRC, who has exhausted at least one prior line of standard systemic therapy for their current malignancy. - Participant with genomic aberrations, including but not limited to BRAFV600E mutations and HER2 amplifications, for which FDA-approved targeted therapies are available, must: - Have received prior treatment with applicable FDA-approved targeted therapies AND - Either have experienced disease progression, be refractory, or be intolerant to directed molecular therapy. - Participant able to provide archival tissue sample or fresh biopsy tissue sample

The main exclusion criteria include but are not limited to the following: - Participant whose CRC tumor tissues have been identified as dMMR or MSI-H - Known history of solid organ or tissue transplant; history of interstitial lung disease or non-infectious pneumonitis. - Untreated central nervous system (CNS) metastatic disease. - Active autoimmune disease that has required systemic treatment within the past 2 years (participants with hormone replacement therapy for adequately controlled endocrinopathy are allowed in the study). - History of recent infection (within 4 weeks of C1D1) considered to be caused by one of the pathogens: HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68. - Known seropositive for human immunodeficiency virus, hepatitis B surface antigen, or antibody to hepatitis C virus with confirmatory testing and requiring anti-viral therapy. - History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome. - Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias. - Congenital long QT syndrome or a corrected QT interval (QTc) ≥480 ms at screening (unless secondary to pacemaker or bundle branch block). - Active second primary malignancy within 3 years of Screening other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, or ductal or lobular carcinoma in situ of the breast