Phase I Dose Escalation of i.v. BI 836909 Monotherapy in Last Line Multiple Myeloma Patients

An Open Label, Phase I, Dose Escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Doses of BI 836909 in Relapsed and/or Refractory Multiple Myeloma Patients

The primary objective of this trial is to determine the maximum tolerated dose (MTD) of BI 836909 administered by continuous i.v. infusion in patients with relapsed and/or refractory multiple myeloma. If the MTD is not reached based on safety findings, a recommended dose for further development will be determined. This will depend on the safety data, pharmacokinetic/pharmacodynamics data and potentially preliminary efficacy data. Secondary objectives are to document the safety and tolerability of BI 836909, to perform pharmacokinetic and pharmacodynamic analyses and to evaluate relevant biological effects in terms of parameters of efficacy.

Inclusion criteria:

• Patients with a documented diagnosis of relapsed and/or refractory multiple myeloma who progressed after at least two prior treatment regimens, including both proteasome inhibitor as well as an immune-modulatory drug at time of screening

• must have measurable disease, defined by one or more of following at time of screening:

  • a serum M protein > 0.5 g/dl measured by serum protein electrophoresis
  • urinary M protein excretion > 200 mg/24 hours
  • serum free light chain (FLC) measurement > 10 mg/dl, provided that the serum FLC ratio is abnormal

• Relapse or progression of disease with an indication for therapy as per investigator´s judgement at time of screening

• ECOG Performance Status 0, 1 or 2 at time of screening

• Age >= 18 years at time of screening

• Written informed consent which is consistent with ICH_GCP guidelines and local legislation

• Able to adhere to the study visit schedule e.g. ability to come to the clinic and to other protocol requirements

• Indwelling central venous catheter or willingness to undergo intra venous central line placement.

Exclusion criteria:

• Plasma cell leukemia
• Extramedullary relapse of multiple myeloma
• Known central nervous system involvement by multiple myeloma
• Last anticancer treatment < 2 weeks prior to visit 1
• Last treatment with a therapeutic antibody less than 6 weeks prior to visit 1
• Prior allogeneic stem cell transplantation or solid organ transplantation
• Autologous bone marrow transplantation < than 90 days at time of treatment start
• Last corticosteroid < 2 weeks prior to visit 1 unless the dose is <= 10 mg/day prednisolone or equivalent
• AST or ALT > 3 x upper limit of normal (CTCAE version 4.03 grade 2 or higher) at time of screening
• Total conjugated bilirubin > 1.5 x upper limit of normal (CTCAE version 4.03 grade 2 or higher) at time of screening
• Absolute neutrophil count < 1.0 x 109/L (without growth factor support) at time of screening
• Platelets < 25 x 109/L (without transfusions) at time of screening
• Calculated GFR < 30 mL/min (Cockcroft-Gault Formula) at time of screening
• Clinical relevant concurrent medical disease or condition which according to the investigator's judgement would either compromise patient safety or interfere with the evaluation of the safety of the test drug, e.g. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy at time of screening
• clinically not controlled chronic or ongoing infectious disease requiring treatment at the time of enrolment or within the previous two weeks
• Active hepatitis B or C, or laboratory evidence for a chronic infection with hepatitis B or C at time of screening; HIV infection at time of screening
• Women of childbearing potential not using highly effective method of birth control during the trial until one year after the last dose. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year)when used consistently and correctly used such as implants, injectables, combined oral contraceptives, intrauterine devises (IUDs), sexual abstinence or vasectomised partner. Barrier methods of contraception are accepted if condom or occlusive cap is used together with spermicides (e.g. foam, gel). Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or postmenopausal (12 months with no menses without an alternative medical cause
• Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial and for a minimum of 6 months after treatment
• Pregnancy or breast feeding
• Known or suspected active alcohol or drug abuse as per investigator's judgement
• Treatment with another investigational drug within the past four weeks before start of therapy or concomitantly with this trial
• Patients with known hypersensitivity to any component of the study drug
• Patients with other malignancies within 5 years at time of screening (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ treated with curative therapy)
• Known autoimmune diseases requiring systemic treatment in past 5 years and interfering with evaluation of study drug
• Pre-existing disorders of the central nervous system