Fig. 8: CDX0239-PBD demonstrates potent in vivo efficacy in ALK-expressing and lorlatinib-resistant neuroblastoma NB-SD xenograft model via intracellular delivery of PBD with subsequent DNA damage and apoptosis.

A Average tumor volume with daily lorlatinib treatments at 10 mg/kg (green line with circles) compared to normal saline vehicle (black line with circles). B Average tumor volume with 3 weekly treatments of 1 mg/kg CDX0239-PBD (blue line with circles) compared to IgG (gray line with squares) and normal saline vehicle (black line with circles). C Survival of xenograft models with daily lorlatinib at 10 mg/kg (green line) compared to normal saline vehicle (black line). D Survival of xenograft models with 3 weekly treatments of 1 mg/kg CDX0239-PBD (blue line) compared to IgG (gray line) and normal saline vehicle (black line). E Western Blot analysis of total ALK, phosphorylated ALK (pALK1604), phosphorylated H2Ax (γH2Ax), cleaved caspase 3 (cCaspase-3), and cleaved PARP (cPARP) in NB-SD xenograft models 3 and 7 days after treatment with 10 mL/kg normal saline vehicle (Veh-D3 and Veh-D7, respectively) or 1 mg/kg CDX0239-PBD (ADC-D3 and ADC-D7, respectively). Average tumor volumes are plotted as mean ± standard deviation with n = 5 mice per treatment condition for all experiments, and each experiment was completed once. Represented data for Western blot experiments has been validated with 2 independent experiments using the same biologic replicate tumor samples. Sample size, datasets, and unprocessed western blot scans are located within the Source Data file. Source data are provided as a Source Data file.