Eligibility requires adults (&ge;18) with IMWG-defined active MM after &ge;3 prior lines (IMiD/PI/anti-CD38) who are transplant-ineligible/post-SCT, excluding those with plasma cell leukemia, active CNS/other malignancies, uncontrolled infections (HIV/HBV/HCV), or recent SCT/radiotherapy (<12/<21 weeks). Phase 2a specifically excludes prior BCMA-targeted therapy exposure.

To measure cell viability, 5,000 cells per well were plated in 96-well plates and incubated with cetuximab, isotype ADC, ADC, or free inhibitor for 96 hours at 37°C. Cell viabilities were detected by CellTiter 96 AQueous One Solution Cell Proliferation Assay (Promega) according to the manufacturer's instructions. Optical absorbance was read on a FLUOstar Omega spectrophotometer (BMG Labtech; RRID:SCR_025024).

Cells were seeded at a density of 2 × 103 cells/well in 90 uL of the respective culture medium. On the following day, cells were exposed to ATACs and incubated at 37°C and 5% CO2 with serial dilutions from 1 × 10-7 mol/L to 1.28 × 10-12 mol/L of the ATACs for 96 hours. Cell proliferation was assessed by the BrdU chemiluminescent ELISA assay (Roche; Sigma-Aldrich/Merck, Cat. # 1669915001), according to the manufacturer's instructions. Luminescence signal intensities were measured directly in a microplate reader (BMG CLARIOstar). Triplicate wells were used for each treatment, and viability was normalized to untreated cells. Error was calculated as the SEM of three independent experiments.

Cells were seeded at a density of 2 × 103 cells/well in 90 uL of the respective culture medium. On the following day, cells were exposed to ATACs and incubated at 37°C and 5% CO2 with serial dilutions from 1 × 10-7 mol/L to 1.28 × 10-12 mol/L of the ATACs for 96 hours. Cell proliferation was assessed by the BrdU chemiluminescent ELISA assay (Roche; Sigma-Aldrich/Merck, Cat. # 1669915001), according to the manufacturer's instructions. Luminescence signal intensities were measured directly in a microplate reader (BMG CLARIOstar). Triplicate wells were used for each treatment, and viability was normalized to untreated cells. Error was calculated as the SEM of three independent experiments.

Cells were seeded at a density of 2 × 103 cells/well in 90 uL of the respective culture medium. On the following day, cells were exposed to ATACs and incubated at 37°C and 5% CO2 with serial dilutions from 1 × 10-7 mol/L to 1.28 × 10-12 mol/L of the ATACs for 96 hours. Cell proliferation was assessed by the BrdU chemiluminescent ELISA assay (Roche; Sigma-Aldrich/Merck, Cat. # 1669915001), according to the manufacturer's instructions. Luminescence signal intensities were measured directly in a microplate reader (BMG CLARIOstar). Triplicate wells were used for each treatment, and viability was normalized to untreated cells. Error was calculated as the SEM of three independent experiments.

Cells were seeded at a density of 2 × 103 cells/well in 90 uL of the respective culture medium. On the following day, cells were exposed to ATACs and incubated at 37°C and 5% CO2 with serial dilutions from 1 × 10-7 mol/L to 1.28 × 10-12 mol/L of the ATACs for 96 hours. Cell proliferation was assessed by the BrdU chemiluminescent ELISA assay (Roche; Sigma-Aldrich/Merck, Cat. # 1669915001), according to the manufacturer's instructions. Luminescence signal intensities were measured directly in a microplate reader (BMG CLARIOstar). Triplicate wells were used for each treatment, and viability was normalized to untreated cells. Error was calculated as the SEM of three independent experiments.

Cells were distributed into 96-well white round-bottom plates, with each well receiving 1000 cells in RPMI-1640 medium supplemented with 10% FBS. Following a 24-hour incubation period, diluted compounds were introduced to the wells. After 144 hours, a CellTiter-Glo luminescent cell viability assay (Promega, Madison, WI, USA) was performed to assess cell viability. The luminescent readings were normalized as percentages relative to untreated cells, and the IC50 values for each compound were determined.

Cells were distributed into 96-well white round-bottom plates, with each well receiving 1000 cells in RPMI-1640 medium supplemented with 10% FBS. Following a 24-hour incubation period, diluted compounds were introduced to the wells. After 144 hours, a CellTiter-Glo luminescent cell viability assay (Promega, Madison, WI, USA) was performed to assess cell viability. The luminescent readings were normalized as percentages relative to untreated cells, and the IC50 values for each compound were determined.