Phase I/II clinical trials of mesothelin-targeted agents
| Agent | Type of clinical trial | Dose and schedule | Patient population | Number of patients | Outcome | References |
|---|---|---|---|---|---|---|
| SS1P (immunotoxin) | Phase I single-agent bolus study | Dose escalation of SS1P given as i.v. infusion QOD | Mesothelin-positive mesotheliomas, and ovarian and pancreatic cancers | 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 mesotheliomas, and 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 patients with malignant mesothelioma 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 a PR. | (18) | |
| SS1P plus paclitaxel, carboplatin, and bevacizumab | SS1P dose escalation with fixed dose of chemotherapy and bevacizumab | Newly diagnosed stage IV lung adenocarcinoma that is mesothelin-positive | 2 | Study 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expected 50% positivity in lung adenocarcinoma and the mesothelin staining was predominantly cytoplasmic (R. Hassan, unpublished data).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 study | Dose-escalation study | Mesothelioma, pancreatic cancer and mesothelin positive lung and ovarian cancer | 24 | MTD 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 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 | (22) |
| Mesothelin specific immune response observed in 5 out of 10 evaluable patients. | ||||||
| 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 1–3 doses of autologous CIR T cells | Progressive malignant pleural mesothelioma | — | Clinical trial opened May 2011 | (24) |
| ADC, 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., 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.