Open-label Study of the Safety and Activity of Oprozomib in Patients with Hematologic Malignancies

Phase 1b • Histologically confirmed diagnosis of a hematologic malignancy, excluding patients with acute leukemia or MDS. • Relapsed after standard therapy for their malignancy and considered to be an appropriate candidate for a Phase 1 clinical study by their treating physician. Phase 2 • Multiple myeloma with measurable disease • Waldenström macroglobulinemia with symptomatic relapse • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. Ethical/Other • Patients must sign a written informed consent form in accordance with federal, local, and institutional guidelines. • Female patients of childbearing potential must have a negative serum or urine pregnancy test and agree to use effective contraception. Male patients must use an effective barrier method of contraception.

• Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy intended to treat underlying malignancy, within 3 weeks prior to first dose or 6 weeks for antibody therapy. • Radiation therapy within 3 weeks prior to first dose. Radioimmunotherapy within 8 weeks prior to first dose. Localized radiation therapy within 1 week prior to first dose. • Immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required). • Prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-vs-host disease (GvHD; as defined in Filipovich 2005). • Evidence of central nervous system (CNS) lymphoma. • Prior treatment with carfilzomib unless in the phase 2. • Major surgery within 3 weeks prior to first dose. • Symptomatic Congestive heart failure, ischemia, conduction abnormalities, or myocardial infarction within 6 months. • Acute active infection requiring systemic antibiotics, antivirals, or antifungals. • Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive. • Active hepatitis A, B, or C infection. • Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose. • Patients with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis. • History of previous clinically significant GI bleed in the last 6 months prior to first dose. • Female patients who are pregnant or lactating.