In the first-in-human study, indatuximab ravtansine (10, 20, 40, 80, 120, 160, 200 mg/m²) was administered to 32 patients on day 1 of each 21-day cycle. The MTD was 160 mg/m². In the phase I/IIa study, indatuximab ravtansine (40, 50, 65, 80, 100, 120, 140, 160 mg/m²) was administered to 35 patients on days 1, 8, and 15 of each 28-day cycle, and the MTD/recommended phase II dose was 140 mg/m².

Eligible relapsed/refractory myeloma patients (≥18 years, ECOG ≤2) must have failed prior therapies (1+ for Len/Dex arm, 2+ for Pom/Dex arm) and comply with REMS programs. Exclusions include recent chemotherapy/radiotherapy (3-6 weeks), active HBV/HCV/HIV, cardiac abnormalities, pregnancy, prior BT062 exposure, or hypersensitivity to biologics. Plasma cell leukemia and recent thromboembolic events (DVT/PE within 3 months) are prohibited.

The study consists of two phases: Phase I (6 months) determines the optimal dose of BT062 combined with lenalidomide/dexamethasone using a standard 3+3 dose escalation design focused on DLTs in cycle 1; Phase IIa (18 months) evaluates treatment response using M-protein and serum free light chain assessments at each 28-day cycle, with supplementary bone marrow/skeletal exams as needed.

Eligible participants must have relapsed/refractory multiple myeloma, prior exposure to immunomodulators/proteasome inhibitors, ECOG ≤2, and adequate organ function. Exclusions include recent chemotherapy/radiotherapy (within 3-6 weeks), active infections (HBV/HCV/HIV), uncontrolled cardiac disease, pregnancy, or concurrent antineoplastic therapies. The study prohibits recent major surgery, investigational agents within 4 weeks, and prior MAb therapy with detectable immune responses (HAHA/HACA/HAMA).

Eligible participants had relapsed/refractory myeloma with prior immunomodulator/proteasome inhibitor exposure, ECOG ≤2, and adequate organ function. Exclusions included recent chemotherapy/radiotherapy (3-6 weeks), active HBV/HCV/HIV, uncontrolled cardiac disease, prior BT062/HAMA/HAHA, or pregnancy. Concomitant antineoplastic therapies and high-dose corticosteroids were prohibited.

BT062 was to be administered as single-dose IV infusions via a 0.22 um in-line filter preferably in a forearm vein, according to medically accepted procedures on Days 1, 8, and 15 of each 28-day cycle. Alternatively BT062 may have been administered through a central venous line or a peripherally inserted central catheter (PICC). Other administration routes were only to be allowed after approval from Biotest. Each subject was to be monitored carefully for the effects of exposure to BT062. No subject was to have received more than 3 doses of BT062 per 28-day treatment cycle.

The study evaluated dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for BT062 in relapsed/refractory multiple myeloma using a 3+3 dose escalation design. DLTs were assessed during the first 28-day cycle, and MTD was defined as the highest dose where <2 of 6 subjects experienced DLTs. Dose escalation stopped if ≥2 DLTs occurred at any level.

Safety and efficacy assessments included qualitative/quantitative toxicities (TEAEs, SAEs), pharmacokinetic properties (Cmax of BT062 conjugate), and anti-tumor activity. Responses were graded per IMWG criteria (sCR, CR, VGPR, PR, MR, SD), with ORR (MR+PR+VGPR+CR+sCR) and CBR (ORR+SD) as key endpoints. Disease progression metrics (TTP, PFS, OS) tracked M-protein increases (≥25%), new lesions, or hypercalcemia.