Table 1.
Phase I/II clinical trials of mesothelin targeted agents
| Agent | Type of clinical trial |
Dose and schedule |
Patient population | No. of patients |
Outcome | Refs. |
|---|---|---|---|---|---|---|
| SS1P (Immunotoxin) | Phase I single agent bolus study | Dose-escalation of SS1P given as i.v. infusion QOD | Mesothelin positive mesotheliomas, ovarian and pancreatic cancer | 34 | MTD 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. study | Dose escalation of SS1P given as c.i. over 10 days | Mesothelin positive mesothelioms, ovarian and pancreatic cancers | 24 | MTD was 25 µg/kg/d given as c.i. over 10 days. No CR 1 PR. | 17 | |
| Phase I SS1P plus pemetrexed and cisplatin | SS1P dose escalation with fixed standard doses of pemetrexed and cisplatin | Chemotherapy naïve malignant mesothelioma patients who are not candidates for curative surgical resection | 19 | Study open to patient accrual. At the MTD 5 out of 7 evaluable patients have had partial response. | 18 | |
| SS1P plus paclitaxel, carboplatin & bevacizumab | SS1P dose escalation with fixed dose of chemotherapy and bevacizumab | Newly diagnosed stage IV lung adenocarcinoma that are mesothelin positive | 2 | Study closed since the incidence of mesothelin positivity was less than the expected 50% positivity in lung adenocarcinoma and the mesothelin staining was predominantly cytoplasmic (Hassan R, unpublished data). | N/R | |
| MORAb-009 (Chimeric mAb) | Phase I single agent study | Dose-escalation study | Mesothelioma, pancreatic cancer and mesothelin positive lung and ovarian cancer | 24 | MTD 200 mg/m2 In patients with mesothelioma treatment with MORAb-009 led to increase in serum CA-125 levels |
19 |
| Phase II MORAb-009 plus gemcitabine | Patients randomized to either gemcitabine alone or gemcitabine plus MORAb-009 | Locally advanced and metastatic pancreatic cancer | N/R | Study closed. Data not yet available. | 20 | |
| Phase II MORAb-009 plus pemetrexed and cisplatin | Single arm study | Newly diagnosed unresectable pleural mesothelioma | N/R | Study is ongoing but closed to new patient accrual. | 21 | |
| CRS-207 (tumor vaccine) | Phase I single agent | Dose-escalation study | Patients with mesothelin expressing cancers | 17 | MTD 1 × 109 cfu Mesothelin specific immune response observed in 5 out of 10 evaluable patients. |
22 |
| Phase II CRS-207 plus GVAX | Patients randomized to GVAX pancreas vaccine versus GVAX pancreas vaccine plus CRS-207 | Previously treated metastatic pancreatic cancer | - | Clinical trial opened August 2011 | 23 | |
| Autologous CIR T cells transfected with anti-mesothelin messenger RNA | Phase I | Patients will receive 1 to 3 doses of autologous CIR T cells | Progressive malignant pleural mesothelioma | - | Clinical trial opened May 2011 | 24 |
| Antibody drug conjugate, BAY 94-9343 | Phase I | BAY 94-9343 given i.v. every 3 weeks | Patients with advanced solid tumors | - | Clinical trial opened September 2011 | 25 |
Abbreviations: c.i., continous infusion; CIR, Chimeric Immune Receptor; CR, complete response; MR, minor response; MTD, maximum tolerated dose; N/R, not reported; PFS, progression free survival; PR, partial response; QOD, every other day; SD, stable disease. .