A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis

Inclusion Criteria:

* Genetic diagnosis of classical familial adenomatous polyposis (FAP) (adenomatous polyposis coli \[APC\] germline mutation or obligate carrier) with disease involvement of the colorectum
* At least 6 polyps greater than or equal to (\>=) 2 millimeters (mm) in diameter in the rectum or colon
* A female participant of childbearing potential must have a negative highly sensitive pregnancy test at screening and within 72 hours prior to the first dose of study drug and must agree to further pregnancy tests during the study
* A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study drug
* Must sign an informed consent form (ICF) indicating he or she understands the purpose of the study and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard of care for the participant's disease

Exclusion Criteria:

* Use of non-steroidal anti-inflammatory drugs (example, aspirin, ibuprofen) exceeding 5 days per month or exceeding the nonprescription dose, unless the participant completes a 4-week washout period prior to the first dose of study drug
* Treatment with other FAP-directed drug therapy (including sulindac or celecoxib), unless completes a 4-week washout period prior to the first dose of study drug
* History of human immunodeficiency virus (HIV)
* History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
* A history of, or ongoing, chronic or recurrent infectious disease including latent or active tuberculosis (TB)