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

Mesothelioma Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Mesothelioma

• NCT number: NCT03436732
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 1
• Start date: February 28, 2018
• Completion date: April 30, 2019