Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma

Purpose: mesothelioma is cancer of the tissue that lines some organs. A new drug, LMB-100, may bind to a protein on mesothelioma tumors and kill cancer cells. But sometimes the body makes antibodies that reduce how well LMB-100 works. Researchers want to see if adding the drug SEL-110 to LMB-100 will prevent these antibodies from forming.

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 ]

Detailed Description

  • 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.

Eligibility

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

« Mesothelioma Clinical Trials Main Page.

Source: the U.S. National Institutes of Health via ClinicalTrials.gov. Last updated: February 28th, 2018.

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Last update: February 19, 2019. 04:08:16 pm.