NCT03436732

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

A Phase I Study of the Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Background: 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. Objective: To learn how safe and tolerable LMB-100 plus SEL-110 is in people with advanced mesothelioma. Eligibility: Adults ages 18 and older who have pleural or peritoneal mesothelioma that has not responded to prior platinum-based therapy Design: Participants will be screened with * Medical history * Physical exam * Blood and urine tests * Sample of tumor tissue. This can be from a previous procedure. * Scan of the chest, abdomen, and pelvis. Participants will lie on a table in a scanner that takes pictures. A special dye may be injected in a vein. * Positron emission tomography (fludeoxyglucose positron emission tomography (FDG-PET)) scan. A sugar attached to a chemical that gives off a signal will be injected before the scan. * Heart function tests The study will be done in 21-day cycles. Participants will get the study drugs for up to 4 cycles. They will get them through an intravenous (IV) catheter (a tube inserted in a vein, usually in the arm): * LMB-100 for about 30 minutes on day 1, day 3, and day 5 of each cycle * SEL-110 for about 1 hour on day 1 of each cycle Participants will get standard medicines to help prevent side effects. Participants will repeat some screening tests during each cycle and about 5 weeks after the last dose of study drug.

Detailed description

Background: * 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. Objectives: -The primary objective of the study is to assess the safety and tolerability of LMB-100 in combination with SEL-110. Eligibility: Primary 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 per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. * 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 Primary Exclusion Criteria: * Known or clinically suspected central nervous system (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 Design: * This is a Phase I, single center, dose escalation study of LMB-100 in combination with SEL-110 * Patients will receive the combination using a dose escalation scheme in which different doses of LMB100 and SEL-110 will be evaluated. * Patients will receive 4 cycles of LMB-100 with SEL-110. A cycle will consist of intravenous (i.v.) infusion of SEL-110 on Day 1 of the cycle followed immediately by an i.v. infusion of LMB-100, then on Days 3 and 5 of the cycle patients will receive an i.v. infusion of LMB-100 only. Treatment cycles will be separated by 21 days.

Conditions

• Mesothelioma

Interventions

Type	Name	Description
DRUG	LMB-100	administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles
DRUG	SEL-110	administered on day 1 of each cycle for up to 4 cycles

Timeline

• Start date: 2018-02-28
• Primary completion: 2019-04-30
• Completion: 2019-04-30
• First posted: 2018-02-19
• Last updated: 2019-11-22
• Results posted: 2019-11-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study