Table 2.

Comparison of SS1P and the redesigned anti-mesothelin immunotoxin RG7787

Targeting moeityAnti-MSLN dsFvHumanized anti-MSLN Fab
PE payloadPE containing Domains II and III (PE38)PE with most of Domain II deleted and Domain III bearing 7 point mutations to remove B-cell epitopes (PE24)
Payload size38 kDa24 kDa
Full molecule size62 kDa72 kDa
Activity in vitroPicomolar range for many tumor cell linesPicomolar range for many tumor cell lines
Mouse MTD0.4 mg/kg i.v. every other day ×3a3.75 mg/kg i.v. every other day ×3a
Efficacy in mouse tumor modelsShrinks A431 epidermoid cancer cells expressing transfected MSLN and complete regressions with chemotherapy (9). Ineffective against KLM1 pancreatic.aDecreases tumor volume of MSLN-positive breast (HCC70), gastric (MKN28), and large lung tumors (H596). Cytostatic in KLM1 pancreatic as single agent, but complete regressions with taxane (10, 11, 19)
Immunogenicity90% of patients make neutralizing antidrug antibodies after 1 cycle (20, 21)Limited reactivity to antidrug antibodies from sera of patients previously treated with SS1P (18)
Current clinical testingPhase II in combination studies with pentostatin and cyclophosphamide (NCT01362790)Phase I for MSLN-positive tumors (NCT02317419)

Abbreviation: MSLN, mesothelin.

  • aUnpublished.