Primary Outcome Measures
- Safety and tolerability [ Time Frame: 4 months after last patient has enrolled ]
- Reporting of adverse events with grade 3 and grade 4 fraction at each dose level
- Maximum tolerated dose [ Time Frame: 21 days after the last patient in the dose escalation cohort has initiated study theapy ]
- Highest tested dose of LMB-100 and SEL-110 at which no more than 1 of 6 subjects experience a dose limiting toxicity
Secondary Outcome Measures
- Descriptive statistics of pharmacokinetic parameters including half life, clearnace, AUC, volume of distribution [ Time Frame: 3 months after last patient enrolled ]
- Fraction of patients with partial or complete response [ Time Frame: 2 years after last patient enrolled ]
- Fraction of patients with detectable LMB-100 in blood after cycle 4 [ Time Frame: 3 months after last patient enrolled ]
- LMB-100 and a closely related immunotoxin also targeting mesothelin have been studied in previous Phase 1 clinical studies for mesothelioma and pancreatic cancer.
- Results from these studies showed that the majority of patients formed anti-drug-antibodies (ADAs) that neutralized subsequent injection of the product making it ineffective.
- In a small subset of patients that did not form ADAs to the product, good response and regression of tumors was seen.
- In a different application SEL-110, a biodegradable nanoparticle containing rapamycin, has been shown in clinical trials to prevent the formation of ADAs to an immunogenic enzyme when co-administered. Preclinical data show that SEL-110 also prevents the formation of ADAs to LMB-100.
- This clinical trial will investigate whether SEL-110 when administered with LMB-100 is able to prevent the formation of ADAs and thus allow patients to receive multiple, effective injections of LMB-100.
- Inclusion Criteria
- Greater than or equal to 18 years of age
- Histologically confirmed epithelial or biphasic pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as >10 mm with spiral CT scan.
- Patients must have had at least one prior chemotherapy regimen that includes pemetrexed and cisplatin or carboplatin. There is no limit to the number of prior chemotherapy regimens received.
- Patients for whom no standard curative therapy exists
- Exclusion Criteria
- Known or clinically suspected CNS primary tumors or metastases including leptomeningeal metastases.
- Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results.
- Evidence of active or uncontrolled infections.
- Live attenuated vaccinations 14 days prior to treatment
- Pregnant women are excluded from this study