Phase 1b/2 Study of Carfilzomib in Relapsed Solid Tumors, Multiple Myeloma, or Lymphoma

Inclusion Criteria: Disease related Phase 1 Subjects (Bolus and Infusion): Solid Tumor: * Histologically confirmed advanced solid tumor * 1 to 3 prior treatment regimens * At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional computed tomography (CT) scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Medical Monitor Multiple Myeloma (MM): * Relapsed and/or refractory multiple myeloma following 2 or more prior treatment regimens. * Measurable disease as indicated by one or more of the following: * Serum M-protein ≥ 1 g/dL * Urine M-protein ≥ 200 mg/24 hr * Serum Free Light Chain: Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal Lymphoma: * Histologically or cytologically confirmed lymphoma. * Patients must have had an initial diagnosis of indolent non-Hodgkin lymphoma (NHL) (including follicular, small lymphocytic, lymphoplasmacytoid, and marginal zone lymphoma), indolent disease that transformed to a more aggressive subtype, as previously described or patients may have mantle cell lymphoma. * Patients are required to have received prior rituximab (alone or combined with other treatment) and are considered refractory to (defined as no response, or progression within 6 months of completing therapy) or intolerant of continued rituximab. * Patients may have received up to a maximum of four prior unique chemotherapy regimens, including if not contra-indicated autologous stem-cell transplantation (ASCT). * For patients to enroll in the expanded dose group for lymphoma, patients must have measurable disease Phase 2 Bolus Subjects: -Histologically confirmed advanced solid tumor diagnosis and: * Non-small cell lung cancer (NSCLC): Failed at least 1 prior platinum-based chemotherapy regimen but not more than 3 prior therapies for metastatic disease * Small cell lung cancer (SCLC): Failed 1 to 3 prior chemotherapy regimens * Ovarian: Failed at least 1 prior platinum-based chemotherapy regimen but not more than 4 therapies for metastatic disease * Renal: Failed at least 2 prior chemotherapy regimens for metastatic disease * Other solid tumor types: Failed at least 1 prior chemotherapy regimen for metastatic or relapsed disease and for which standard of care therapy is no longer effective or does not exist * At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional CT scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per RECIST criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Medical Monitor Demographic * Males and females ≥ 18 years of age * Life expectancy of more than 3 months * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Laboratory * Adequate hepatic function, with bilirubin 1.5 times the upper limit of normal (ULN), and alanine aminotransferase (ALT) 3 times ULN * Absolute neutrophil count (ANC) \> 1000/mm³, hemoglobin ≥ 8 gm/dL for solid tumors or 7.0 gm/dL for MM, and platelet count ≥ 100,000/mm³ for solid tumors or ≥ 30,000/mm³ for MM. * Subjects should not have received platelet transfusions for at least 1 week prior to screening * Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for ≥ 2 weeks * Subjects may receive red blood cell (RBC) transfusions or receive supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines * Calculated or measured creatinine clearance (CrCl) of ≥ 20 mL/minute calculated using the formula of Cockcroft and Gault. Subjects with calculated CrCl \< 20 mL/min may be allowed, only with prior approval by the Medical Monitor. Ethical/Other * Written informed consent in accordance with federal, local, and institutional guidelines * Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose and agree to use dual methods of contraception during the study and for 3 months following the last dose of study drug. Post-menopausal females (\> 45 years old and without menses for \> 1 year) and surgically sterilized females are exempt from these requirements. Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential. Exclusion Criteria: Disease Related * Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy, within 3 weeks prior to first dose or 6 weeks for antibody therapy * Radiation therapy or immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required); localized radiation therapy within 1 week prior to first dose * Subjects with prior brain metastases are permitted, but must have completed treatment and have no evidence of active central nervous system (CNS) disease for at least 4 weeks prior to first dose * For lymphoma patients; patients with prior stem cell transplant 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-versus-host disease (GVHD) * Evidence of CNS lymphoma * Participation in an investigational therapeutic study within 3 weeks prior to first dose * Prior treatment with carfilzomib Concurrent Conditions * Major surgery within 3 weeks prior to first dose * Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 3 months prior to first dose * Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose * Known or suspected human immunodeficiency virus (HIV) infection or subjects 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 * Subjects with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis * Subjects at risk\* in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment * High risk for Tumor Lysis Syndrome. Ethical / Other * Female subjects who are pregnant or lactating * Any clinically significant psychiatric or medical condition that in the opinion of the Investigator could interfere with protocol adherence or a subject's ability to give informed consent