Table 1.

Phase I/II clinical trials of mesothelin-targeted agents

AgentType of clinical trialDose and schedulePatient populationNumber of patientsOutcomeReferences
SS1P (immunotoxin)Phase I single-agent bolus studyDose escalation of SS1P given as i.v. infusion QODMesothelin-positive mesotheliomas, and ovarian and pancreatic cancers34MTD of SS1P was 45 μg/kg i.v. QOD × 3 doses. DLT was pleuritis. 4 MR and 18 SD out of 33 pts.(16)
Phase I single-agent c.i. studyDose escalation of SS1P given as c.i. over 10 daysMesothelin-positive mesotheliomas, and ovarian and pancreatic cancers24MTD was 25 μg/kg/d given as c.i. over 10 days. No CR, 1 PR.(17)
Phase I SS1P plus pemetrexed and cisplatinSS1P dose escalation with fixed standard doses of pemetrexed and cisplatinChemotherapy-naïve patients with malignant mesothelioma who are not candidates for curative surgical resection19Study open to patient accrual. At the MTD, 5 out of 7 evaluable patients have had a PR.(18)
SS1P plus paclitaxel, carboplatin, and bevacizumabSS1P dose escalation with fixed dose of chemotherapy and bevacizumabNewly diagnosed stage IV lung adenocarcinoma that is mesothelin-positive2Study closed because the incidence of mesothelin positivity was less than the expected 50% positivity in lung adenocarcinoma and the mesothelin staining was predominantly cytoplasmic (R. Hassan, unpublished data).N/R
MORAb-009 (chimeric mAb)Phase I single-agent studyDose-escalation studyMesothelioma, pancreatic cancer and mesothelin positive lung and ovarian cancer24MTD 200 mg/m2(19)
In patients with mesothelioma, treatment with MORAb-009 led to an increase in serum CA-125 levels.
Phase II MORAb-009 plus gemcitabinePatients randomized to either gemcitabine alone or gemcitabine plus MORAb-009Locally advanced and metastatic pancreatic cancerN/RStudy closed. Data not yet available.(20)
Phase II MORAb-009 plus pemetrexed and cisplatinSingle arm studyNewly diagnosed unresectable pleural mesotheliomaN/RStudy is ongoing but closed to new patient accrual.(21)
CRS-207 (tumor vaccine)Phase I single agentDose-escalation studyPatients with mesothelin-expressing cancers17MTD 1 × 109 cfu(22)
Mesothelin specific immune response observed in 5 out of 10 evaluable patients.
Phase II CRS-207 plus GVAXPatients randomized to GVAX pancreas vaccine versus GVAX pancreas vaccine plus CRS-207Previously treated metastatic pancreatic cancerClinical trial opened August 2011(23)
Autologous CIR T cells transfected with anti-mesothelin messenger RNAPhase IPatients will receive 1–3 doses of autologous CIR T cellsProgressive malignant pleural mesotheliomaClinical trial opened May 2011(24)
ADC, BAY 94-9343Phase IBAY 94-9343 given i.v. every 3 weeksPatients with advanced solid tumorsClinical trial opened September 2011(25)

Abbreviations: c.i., continuous infusion; CIR, chimeric immune receptor; CR, complete response; MR, minor response; N/R, not reported; PR, partial response; QOD, every other day; SD, stable disease.