Study of BTK Inhibitor, Ibrutinib in Combination With Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma

Inclusion Criteria

• Measurable disease of MM as defined by at least ONE of the following:
• Serum monoclonal protein (SPEP) ≥1 g/dL
• Urine M-protein ≥200 mg/24 hrs
• Serum free light chain (SFLC): involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal kappa to lambda serum free light chain ratio
• Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies, including an immunomodulator and bortezomib and had either no response or documented disease progression (according to IMWG criteria) to the most recent treatment regimen
• Adequate hematologic, hepatic, and renal function
• ECOG performance status of 0-2

Inclusion Criteria for Phase 2 Sub-study Cohort:

• Must meet all inclusion criteria defined in main study and in addition the following criteria must be met:
• Subject must have received a regimen containing carfilzomib in combination with dexamethasone as their most recent line of therapy and have:
• Achieved less than a partial response (<PR) following at least 4 cycles and are without evidence of progression disease (PD).

OR

• Disease progression following an initial confirmed response of MR or better to the combination (according to IMWG response criteria).

Exclusion Criteria

• Subject must not have primary refractory disease
• Plasma cell leukemia, primary amyloidosis or POEMS syndrome
• Unable to swallow capsules or disease significantly affecting gastrointestinal function
• Requires anti-coagulation with warfarin or a vitamin K antagonist
• Requires treatment with strong CYP3A inhibitors

Exclusion Criteria for Phase 2 Sub-study Cohort:

• Must not meet any exclusion criteria defined in main study except for exclusion criteria "Subject must not have primary refractory disease" which is related to prior carfilzomib