Comparison of SS1P and the redesigned anti-mesothelin immunotoxin RG7787
| SS1P | RG7787 | |
|---|---|---|
| Targeting moeity | Anti-MSLN dsFv | Humanized anti-MSLN Fab |
| PE payload | PE 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 size | 38 kDa | 24 kDa |
| Full molecule size | 62 kDa | 72 kDa |
| Activity in vitro | Picomolar range for many tumor cell lines | Picomolar range for many tumor cell lines |
| Mouse MTD | 0.4 mg/kg i.v. every other day ×3a | 3.75 mg/kg i.v. every other day ×3a |
| Efficacy in mouse tumor models | Shrinks A431 epidermoid cancer cells expressing transfected MSLN and complete regressions with chemotherapy (9). Ineffective against KLM1 pancreatic.a | Decreases 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) |
| Immunogenicity | 90% 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 testing | Phase II in combination studies with pentostatin and cyclophosphamide (NCT01362790) | Phase I for MSLN-positive tumors (NCT02317419) |
Abbreviation: MSLN, mesothelin.
↵aUnpublished.