Inclusion Criteria:
Relapsed/Refractory Arm
Inclusion Criteria:
* Pathologically confirmed MCL (in tumor tissue), with documentation of either overexpression of cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR).
* At least 1 measurable site of disease on cross-sectional imaging (CT).
* At least 1, but no more than 5, prior treatment regimens for MCL.
* Failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen.
* Subjects must have adequate fresh or paraffin embedded tissue.
* Adequate hematologic, hepatic and renal function.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of \<= 2.
Exclusion Criteria:
* History or current evidence of central nervous system lymphoma.
* Concurrent enrollment in another therapeutic investigational study or prior therapy with ibrutinib or other BTK inhibitors.
* Prior treatment with venetoclax or other BCL2 inhibitors.
* Anticancer therapy including chemotherapy, radiotherapy, small molecule and investigational agents \<= 21 days prior to receiving the first dose of study drug.
* Treatment with any of the following within 7 days prior to the first dose of study drug: moderate to strong cytochrome P450 3A (CYP3A) inhibitors or strong CYP3A inducers.
Treatment Naïve Arm
Inclusion Criteria:
* Pathologically confirmed treatment-naive MCL (tumor tissue), with documentation of either overexpression of cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14), as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR).
* Men and women ≥18 years of age with a TP53 mutation.
* At least 1 measurable site of disease by CT.
* Must have adequate fresh or paraffin-embedded tissue.
* Eastern Cooperative Oncology Group (ECOG) performance status score 0 to \<= 2.
* Adequate hematologic, hepatic, and renal function.
Exclusion Criteria:
* Blastoid variant of MCL
* History or current evidence of CNS lymphoma.
* Concurrent enrollment in another therapeutic investigational study or prior therapy including ibrutinib or other BTK inhibitors.
* Prior treatment with venetoclax or other BCL2 inhibitors.
* Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.
* Clinically significant infection requiring IV systemic treatment that was completed \<=14 days before the first dose of study drug.
* Any uncontrolled active systemic infection.
* Known bleeding disorders (eg, von Willebrand's disease or hemophilia).
* History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
* History of HIV or active HCV or HBV.
* Major surgery within 4 weeks of the first dose of study drug.
* Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the participant's safety or put the study outcomes at undue risk.
* Currently active, clinically significant cardiovascular disease; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
* Unable to swallow capsules or tablets, or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
* Treatment with any of the following within 7 days prior to the first dose of study drug: Moderate or strong cytochrome P450 3A (CYP3A) inhibitors or moderate or strong CYP3A inducers.
* Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects with known risk factors (as defined by high tumor burden and/or diminished renal function, as detailed in "Study Design" section above) for TLS.
* Chronic liver disease with hepatic impairment Child-Pugh class B or C.
* Unwilling or unable to participate in all required study evaluations and procedures.
* Known hypersensitivity to the active ingredient or other components of one or more study drugs.
