A Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma

An Open Label, Dose Escalation, Multicenter Phase 1/2 Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma

The purpose of this study is to assess the safety and benefits of the investigational study drug, KW-2478, when given with bortezomib (Velcade®), a drug approved for the treatment of Multiple Myeloma (MM).

The primary objectives:

• To establish the safety, tolerability, and recommended Phase II dose (RP2D) of KW-2478 in combination with bortezomib (Phase I);
• To assess the overall response rate (ORR) when subjects with advanced MM are treated (Phase II).

The secondary objectives:

• To characterize the Pharmacokinetic (PK) and Pharmacodynamic (PD) of KW-2478 with bortezomib (Phase I only);
• To evaluate for preliminary evidence of efficacy (Phase I);
• To determine progression free survival (PFS) and duration of response of KW-2478 with bortezomib (Phase II).

This is a multicenter, open label, dose escalation, Phase I / II study in subjects with relapsed and/or refractory MM. Up to 24 subjects to be enrolled in the Phase I to determine the RP2D. Up to 77 additional evaluable subjects to be enrolled in Phase II for a maximum up to 101 subjects treated in the study. Study centers in the USA and the UK will participate in Phase I and II. Centers in the Philippines will be participating in Phase II only. The planned enrollment period is 22 months and the planned study duration is 28 months.

Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects with a confirmed diagnosis of Multiple Myeloma who have had one and no more than three prior regimens for MM to which they did not respond (failed) or from which they have relapsed.
2. Signed either an IRB or IEC approved informed consent
3. ECOG performance status of ≤ 2
4. Life expectancy of at least 3 months
5. M protein in either serum or urine, or free light chains if not measurable M protein in serum or urine, and clonal bone marrow plasma cells > 10%, and evidence of end organ damage
6. Adequate hematologic status, liver and renal function
7. Subjects of reproductive potential must agree to follow accepted pregnancy prevention methods during the study.

Exclusion Criteria:

1. No anti-cancer treatment for ≥ 4 weeks and no bortezomib treatment ≥ 60 days prior to receiving study drug
2. Any other severe, acute or chronic illness
3. No other prior or concurrent malignancy
4. No immunosuppressant therapy