• To determine the safety and tolerability of human Anti-KIR (1-7F9), a fully human mAb, in subjects with relapsed or refractory multiple myeloma (MM) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  

• To assess pharmacokinetic (PK) parameters of Anti-KIR (1-7F9) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• To assess pharmacodynamic (PD) parameters of Anti-KIR (1-7F9) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• To determine early signs of clinical efficacy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  

Drug: Anti-KIR (1-7F9)
human monoclonal antibody

Trial Design:

The trial is an open-label, dose-escalation trial to determine the safety and tolerability of Anti-KIR (1-7F9) in subjects with relapsed or refractory multiple myeloma. A 3+3 design will be employed for the first dosing cycle at each dose level. The 7 planned dose levels are 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg. The subjects will receive up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks. Safety, toxicity, PK and PD obtained in the first 4 weeks after dosing per group will be the basis for dose-escalation decisions. There will be follow-up visits every week the one month after the first administration and every two weeks following the second, third and fourth administrations. After the last administration there will be follow-up visits every month until KIR occupancy is no longer detected.

Inclusion Criteria:

1. Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
2. Symptomatic multiple myeloma diagnosis according to standard guidelines
3. Relapse or progression after at least one prior systemic treatment regimen for MM, and for which no approved treatment is available or clinically indicated
4. Full recovery from acute toxicities of prior anti-MM therapies
5. Peripheral blood NK cells >0.1x109/L
6. Detectable binding of Anti-KIR (1-7F9) to subject NK cells
7. Age ≥ 18 years
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
9. No major organ dysfunction as judged by the investigator

10. Clinical laboratory values at screening:

    • serum creatinine < grade 2 toxicity i.e. 1.5x upper limit of institutional normal value
    • total bilirubin < 1.5x upper limit of institutional normal value
    • AST < or = 3x upper limit of institutional normal value
    • ANC>1.2 x109/L
    • Platelets >70x109/L

Exclusion Criteria:

1. Known or suspected allergy to trial product or related products
2. Previous participation in this trial (screened)
3. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (appropriate methods include abstinence and the following methods: diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives)
4. Male subjects who are sexually active and have not been surgically sterilized must be informed that they must either use a condom during intercourse, ensure that their partners practices contraception, or they must refrain from sexual intercourse during the study and until 1 month after completion of the trial.
5. The receipt of any investigational drug within a time frame prior to this trial as judged by the investigator
6. Current treatment with any other anti-MM therapy, including radiation
7. Radiotherapy against bone lesions within the last 4 weeks or against visceral lesions within the last 8 weeks prior to screening
8. Last dose of cytotoxic chemotherapy (including Revlimid, excluding thalidomide or bortezomib) or corticosteroids (including dexamethasone) within last 28 days prior to screening
9. Thalidomide and bortezomib treatment within last 14 days prior to screening
10. Subjects with non-secretory multiple myeloma
11. Subjects on dialysis
12. Use of myeloid growth factor in the last 28 days prior to screening
13. G-CSF treatment within the last 28 days prior to screening
14. Systemic steroid treatment within 4 weeks prior to screening
15. Active autoimmune disease
16. Active infectious disease as judged by the investigator
17. New York Heart Association (NYHA) class III-IV heart failure
18. Severe neurological / psychiatric disorder as judged by the investigator
19. HIV / chronic hepatitis infection with evidence of active liver inflammation
20. Clinical evidence of an active second malignancy
21. Subjects with a history of allogenic transplantation
22. Subject who have undergone autologous transplantation within the last 3 months
23. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
24. Other medical conditions that in the opinion of the investigator disqualify the subject for inclusion