Fig. 5: Vartumab ADC efficacy and safety in vivo.
From: Preclinical profiling of antibody drug conjugates targeting oncofetal chondroitin sulfate
a Tumor burden (mean ± SEM mm3) of all groups until first death (n = 5 each group) where melanoma A375-bearing mice were treated with CDCs and ADCs. Vehicle is PBS. Red arrows indicate days of treatment. Vartumab groups are also shown in focus, for dose differentiation in tumor burden. Weights are shown for Vartumab groups and the vehicle. At the end of the study, ADC MMAE groups had 4/5 and 5/5 tumor-free, while ADC DXd groups had 0/5 and 5/5 tumor-free, for 1.6 nmol toxin and 3.2 nmol toxin, respectively. All ADC-treated groups had significant tumor reduction compared to their corresponding controls (p < 0.0001 for all group x day interaction terms). Comparison between 1.6 nmol toxin ADC-MMAE and ADC-DXd revealed greater efficacy of ADC-MMAE (p < 0.0001), while at 3.2 nmol toxin there was no significant difference between ADC-MMAE and ADC-DXd (p = 0.681). b Tumor burden (mm3) and weights of non-small cell lung NCI-H1975-bearing mice treated with CDC-MMAE and ADC-MMAE (n = 5 each group). Vehicle is PBS. Red arrows indicate days of treatment. At the end of the study, the ADC-MMAE group had 1/5 tumor-free. ADC-MMAE showed significantly improved efficacy over CDC-MMAE (p < 0.0001). c Tumor burden of melanoma A375-bearing mice treated with ADC-MMAE and ADC-MMAF at 2.1 nmol toxin (n = 5 each group). Vehicle is PBS. Red arrows indicate days of treatment. At the end of the study ADC-MMAE group had 5/5 tumor-free, and the ADC-MMAF group had 0/5 tumor-free. ADC-MMAF was significantly less effective than ADC-MMAE (p < 0.0001). d Tumor burden (mm3) of melanoma A375-bearing mice treated with ADC-MMAE at 2.1nmol toxin (n = 5 each group). Vehicle is PBS. Red arrows indicate days of treatment. At the end of the study, the ADC-MMAE group had 1/5 tumor-free. e Tolerability of Vartumab ADC-MMAE assessed by measuring the weight of rats treated at 0.5 mg/kg or 5 mg/kg for multiple doses (n = 2 per group, one rat in 0.5 mg/kg was euthanized due to improper vein injection). Vehicle is PBS. f Hematology profile from rats treated with 0.5 mg/kg or 5 mg/kg Vartumab ADC-MMAE from (e). Following two treatments and 2 weeks after the end of treatment. g Representative hematoxylin and eosin staining of liver, kidney, and heart of rats following treatment with 5 mg/kg Vartumab ADC MMAE or vehicle. The scale bar represents 100 µm. For a–c statistical analyses were performed using a linear mixed-effects model in R, modeling tumor volume over time as a function of treatment group, time, and their interaction, with mouse ID as a random effect. Significance was assessed using Satterthwaite’s method (lmerTest).
