Safety and Dose Determining Multi-dose Study of BT062 in Patients With Relapsed or Refractory Multiple Myeloma

The primary safety variable was to determine the incidence of DLTs in subjects with relapsed or relapsed/refractory multiple myeloma treated with BT062.

Time frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)

Population: The Safety population included all subjects who were enrolled and received at least~1 dose of BT062 (n = 35).

The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD. Only DLTs occurring in cycle 1 for each subject were counted in the dose escalation decisions. Three subjects were treated at the first or newest dose level as available. If none of the 3 subjects experienced a DLT during Cycle 1, three subjects could be treated at the next dose level as available. In case of a DLT the cohort was expanded to up to 6 subjects. If not more than 1 of these 6 subjects experienced a DLT during Cycle 1, a first subject could be treated at the next dose level. If 2 or more of the 6 subjects experienced a DLT during Cycle 1 the dose escalation was stopped. The highest dose level at which \< 2 of 6 subjects experienced a DLT is defined as the MTD.

Time frame: First 28-day cycle

sCR:CR+normal FLC+absence of clonal cells in BM; CR:Negative immunofixation,disappearance of soft tissue plasmacytomas +≤5% plasma cells in BM+normal FLC; VGPR:M-protein detectable by immunofixation,not on electrophoresis or 90% or greater reduction in serum M-protein+urine M-protein level \<100mg per 24h,\>90% decrease in the difference between involved/uninvolved FLC; PR:≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to \<200 mg per 24 h or ≥50% decrease in the difference between involved/uninvolved FLC or ≥50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was ≥30%, ≥50% size reduction of soft tissue plasmacytomas; MR:25%-49% reduction of serum M-protein+reduction in 24h urinary M-protein by 50-89%(still \>200 mg/24h),25-49% soft tissue plasmacytomas size reduction,no increase in size or number of lytic bone lesions; SD:no response or PD ORR: %of subjects with MR+PR+VGPR+CR+sCR CBR:ORR + %of subjects with SD.

Time frame: On day 1 of each treatment cycle (on a monthly basis) starting with first study drug administration until Close Out visit (average 3.84 months).

Population: ITT: The Intention-to-treat (ITT) population included all subjects who were enrolled in the study and received at least 1 dose of BT062 and who had any post-Baseline evaluations or data. One subject did not have at least one post-injection assessment of the treatment response and was excluded from both the ITT and PP populations (n = 34).

Multi-dose Pharmacokinetics properties of BT062 after intravenous (IV) Administration of escalating doses of BT062 as assessed by measuring intact BT062 conjugate. Please note that not all subjects reached Cycle 4 due to early termination . A lower number of samples could be analyzed for Cycle 4.

Time frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months).

Population: Safety Population: The Safety population included all subjects who were enrolled and received at least~1 dose of BT062 (n = 35).

Qualitative and quantitative toxicities assessed by incidence of adverse events and by clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results. The incidence of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs).

Time frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)

Population: Safety Population: The Safety population included all subjects who were enrolled and received at least 1 dose of BT062 (n = 35).

Progressive disease Requires any one or more of the following: Increase of ≥ 25% from baseline in * Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL) (increases of ≥ 1 g/dL are sufficient to define relapse if starting M-component is ≥ 5 g/dL). * Urine M-component and/or (the absolute increase must be ≥ 200mg/24h). Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL. Bone marrow plasma cell percentage: the absolute % must be ≥ 10% (relapse form CR as a 5% cutoff instead of 10%). Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/l) that can be attributed solely to the plasma cell proliferative disorder.

Time frame: Starting with first study drug administration until death or 3 years from first study treatment.

Population: The Intention-to-treat (ITT) population included all subjects who were enrolled in the study and received at least 1 dose of BT062 and who had any post-Baseline evaluations or data (n = 34).