NCT02798536

Mesothelin-Targeted Immunotoxin LMB-100 in People With Malignant Mesothelioma

A Phase I Study of the Mesothelin-Targeted Immunotoxin LMB-100 With or Without Nab-Paclitaxel (Abraxane) in Patients With Malignant Mesothelioma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Background: LMB-100 is a man-made protein. It is attracted to the mesothelin protein. This is found in many tumors, including mesothelioma. But it is found in only a very small number of normal tissues. After binding to mesothelin on tumors, LMB-100 attacks and kills cancer cells. Researchers want to test LMB-100 in people with advanced mesothelioma. Objective: To find a safe dose and anti-tumor activity of LMB-100 for people with advanced mesothelioma. Eligibility: Adults ages 18 and older with: Advanced pleural or peritoneal mesothelioma that has not responded to platinum-based therapy Adequate organ function Design: Participants will be screened with: Samples of tumor tissue or tumor fluid. These can be new or from a previous procedure. Medical history Physical exam Blood, urine, and heart tests Chest x-rays Computed tomography (CT) or magnetic resonance imaging (MRI) scans Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans Participants will get LMB-100 on days 1, 3, and 5 of each 21-day cycle. It will be given through an intravenous (IV) catheter, a tube inserted in an arm vein. They will get standard medicines before each infusion to help prevent side effects. Each infusion lasts about 30 minutes. They will be monitored for up to 2 hours after. During each cycle, participants will repeat the screening tests. Participants will get the study drug for up to 4 cycles or until their disease worsens or they have intolerable side effects. About 4-6 weeks after their last infusion, participants will have a follow-up visit. They will repeat the study tests. Participants will have follow-up scans every 6 weeks until their disease gets worse. Participants will be called about once a year to see how they are doing.

Detailed description

Background: * Although mesothelioma patients with a limited tumor burden may benefit from surgical resection, most patients have advanced disease at diagnosis and are not candidates for cytoreductive surgery. * For mesothelioma patients who are not eligible for curative surgery, the median survival with supportive care alone is 6 months whereas with the current standard treatment, a combination of cisplatin and pemetrexed, the median survival is 12 months. * Mesothelin, a tumor differentiation antigen, is expressed in over 95% of epitheloid mesothelioma. Mesothelin is a suitable candidate for targeted therapy due to its very limited expression in normal human tissue and its high expression in several tumors including mesothelioma. * LMB-100 is a novel recombinant anti-mesothelin immunotoxin developed for the treatment of patients with solid tumors that express mesothelin. Mesothelin is targeted by linking a humanized fragment of the anti-mesothelin Fab to a de-immunized Pseudomonas exotoxin (PE). * The clinical use of first generation immunotoxins such as SS1P was hampered mainly by their high immunogenicity. LMB-100 is a next generation PE-fusion protein that has been protein-engineered to maximally reduce its immunogenicity. LMB-100 has shown broad activity against different mesothelin expressing cancer cell lines and tumor xenograft models. Objectives: Phase 1 To identify the recommended phase 2 dose (RP2D) of LMB-100 in patients with treatment refractory advanced epithelioid or biphasic mesothelioma and evaluate potential efficacy of the identified RP2D. -Phase 2 To determine the efficacy of LMB-100 with respect to objective response rate in patients with treatment refractory advanced epithelioid or biphasic mesothelioma. Eligibility: * Age greater than or equal to 18 years * Histologically confirmed advanced pleural or peritoneal mesothelioma * Subjects must have had at least 1 prior chemotherapy regimen with last dose of previous therapy occurring at 3 weeks before the start of study treatment * Adequate organ function * Participants with central nervous system (CNS) metastases or prior pneumonectomy are excluded Design: * This is a Phase I, open-label study to evaluate the safety, pharmacokinetics, and activity of LMB-100 in patients with treatment refractory advanced epithelioid or biphasic mesothelioma. * LMB-100 will be administered intravenously on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles * Tumor response will be assessed after every 2 cycles * Optional tumor biopsies may be collected at baseline and after 2 cycles of therapy * The accrual ceiling will be set at 30

Conditions

• Mesothelioma

Interventions

Type	Name	Description
DRUG	LMB-100	Administered intravenous (IV) on days 1, 3 and 5 of a 21 day cycle for up to 4 cycles (Arms A1 and A2) or 2 cycles (Arms B1 and B2)
DRUG	nab-paclitaxel	Arms B1 and B2 only. Administered intravenous (IV) on days 1 and 8 of each 21 day cycle for up to 6 cycles

Timeline

• Start date: 2016-07-27
• Primary completion: 2017-07-20
• Completion: 2022-04-21
• First posted: 2016-06-14
• Last updated: 2022-08-23
• Results posted: 2022-08-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study