1. Men and women, aged 18 or older (except in South Korea, aged 19 or older). 2. Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or t(11,14). 3. Have received at least 1 but no more than 3 prior systemic treatment regimens. a. Subjects in Cohort 1 will have previously received ibrutinib. b. Subjects in Cohort 2 will not have previously received a BTK inhibitor (eg, ibrutinib). 4. Documented failure to achieve at least PR with or documented disease progression after the most recent treatment regimen. 5. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of e" 1 lesion that measures > 1.5 cm in the LDi and e" 1.0 cm in the longest perpendicular diameter as assessed by CT or MRI. 6. Subjects must be willing to undergo an incisional, excisional, or core needle lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival tissue 7. Life expectancy > 3 months. 8. ECOG performance status 0 to 2 (see Appendix C). 9. Adequate hematologic, hepatic, and renal function (values must not be achieved with growth factors): a. ANC e" 1.0 × 109/L. b. Hemoglobin e" 8.0 g/dL. c. Platelet count e" 50 × 109/L. d. Total bilirubin d" 1.5 × ULN. e. ALT/AST d" 3.0 × ULN or d" 5 × ULN in the presence of liver metastases. f. Calculated creatinine clearance e" 50 mL/min by the Cockcroft-Gault Equation (Cockcroft and Gault 1976) or the estimated glomerular filtration rate e" 50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula. 10. Willingness to avoid pregnancy or fathering children based on the criteria below: a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR e" 12 months of amenorrhea and at least 45 years of age). b. Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subject and their understanding confirmed. c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through at least 93 days after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subject and their understanding confirmed.

1. History of central nervous system lymphoma (either primary or metastatic). 2. Prior treatment with idelalisib, other selective PI3K´ inhibitors, or a pan-PI3K inhibitor. 3. Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment. 4. Active graft-versus-host disease. 5. Use of immunosuppressive therapy within 28 days of the date of study treatment administration. Immunosuppressive therapy includes, but is not limited to, cyclosporine A, tacrolimus, or high-dose corticosteroids. Subjects receiving corticosteroids must be at a dose of d" 10 mg/day prednisone (or equivalent) within 7 days of the date of first study treatment administration. 6. Receipt of anticancer medications or investigational drugs within the following intervals before the first dose of study treatment: a. < 10 weeks from completion of any radio- or toxin-immunoconjugates. b. < 6 weeks for mitomycin-C or nitrosoureas. c. < 4 weeks for immunotherapy. d. < 3 weeks for radiotherapy. e. < 3 days for ibrutinib. f. < 2 weeks for any investigational agent or other anticancer medications. 7. Inadequate recovery from toxicity and/or complications from a major surgery before the date of the first dose of study treatment. 8. Prior treatment-related toxicities have not resolved to NCI CTCAE v4.03 (NCI 2010) d" Grade 1 before the date of the first dose of study treatment except for stable chronic toxicities (Grade d" 2) not expected to resolve (eg, stable Grade 2 peripheral neurotoxicity). 9. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization). 10. Use or expected use during the study of any prohibited medications, including potent CYP3A4 inhibitors or inducers (see Appendix B) within 14 days or 5 half-lives (whichever is longer) before the date of study treatment administration. 11. Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, GI, endocrine, pulmonary, neurological, cerebral, or psychiatric disease. 12. Current or previous other malignancy within 3 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval. 13. History of stroke or intracranial hemorrhage within 6 months of the date of study treatment administration. 14. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 30 days of study treatment. 15. Known HIV infection or positivity on immunoassay. Note: HIV screening test is optional for subjects enrolled in the United States, but subjects with known HIV infection in the United States will be excluded. 16. Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for HBV-DNA, these subjects should be considered for prophylactic antiviral therapy. Subjects positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA 17. Clinically significant cardiac disease, including unstable angina, acute myocardial infarction, and/or cardiac conduction issues within 6 months of the date of study treatment administration 18. Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia. 19. Presence of an abnormal ECG that is clinically meaningful. Screening QTc interval > 450 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is > 450 milliseconds, the subject may enroll if the average QTc for 3 ECGs is < 450 milliseconds. 20. Unable to swallow and retain oral medication, malabsorption syndrome, disease significantly affecting GI function, total resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. 21. Known hypersensitivity or severe reaction to INCB050465 or its excipients (refer to the IB). 22. History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis. 23. Currently pregnant or breastfeeding. 24. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits, pose a significant risk to the subject, or interfere with interpretation of study data. 25. Inability to comprehend or unwilling to sign the ICF (See Section 7.1).