Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)

This is a Phase 2, open-label, nonrandomized, multicenter, monotherapy study in subjects
with histologically documented MCL who have relapsed after ≥ 1 (but not > 5) prior treatment
regimens. All subjects meeting eligibility criteria will receive PCI-32765 capsules at a
dosage of 560 mg/day once daily for a 28-day cycle until disease progression, unacceptable
toxicity, or enrollment in a long-term extension study, whichever occurs earlier.

Inclusion Criteria:

- Men and women ≥ 18 years of age

- ECOG performance status of ≤ 2

- Pathologically confirmed MCL, with documentation of either overexpression of cyclin
D1 or t(11;14), and measurable disease on cross sectional imaging that is ≥ 2 cm in
the longest diameter and measurable in 2 perpendicular dimensions

- Documented failure to achieve at least partial response (PR) with, or documented
disease progression disease after, the most recent treatment regimen

- At least 1, but no more than 5, prior treatment regimens for MCL (Note: Subjects
having received ≥2 cycles of prior treatment with bortezomib, either as a single
agent or as part of a combination therapy regimen, will be considered to be
bortezomib-exposed.)

- Willing and able to participate in all required evaluations and procedures in this
study protocol including swallowing capsules without difficulty

- Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (in accordance
with national and local subject privacy regulations)

Major exclusion criteria:

- Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic
anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10
weeks, radiation therapy within 3 weeks, or major surgery within 2 weeks of first
dose of study drug

- Any life-threatening illness, medical condition or organ system dysfunction which, in
the investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue
risk

- Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart
Association Functional Classification

- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel or ulcerative colitis, symptomatic
inflammatory bowel disease, or partial or complete bowel obstruction

- Any of the following laboratory abnormalities:

1. Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is
documented bone marrow involvement

2. Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion
support unless there is documented bone marrow involvement

3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0
x upper limit of normal (ULN)

4. Creatinine > 2.0 x ULN