Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
Same as current

Summary

Conditions
Mesothelioma
Type
Interventional
Phase
Phase 1
Design
Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

Background: LMB-100, and a closely related immunotoxin, SS1P, also targeting mesothelin, given intravenously, have been studied in Phase 1 clinical studies for mesothelioma and pancreatic cancer. LMB-100 given intravenously, results in systemic inflammation in patients, but as a single agent has lim...

Background: LMB-100, and a closely related immunotoxin, SS1P, also targeting mesothelin, given intravenously, have been studied in Phase 1 clinical studies for mesothelioma and pancreatic cancer. LMB-100 given intravenously, results in systemic inflammation in patients, but as a single agent has limited anti-tumor efficacy. Almost all patients develop neutralizing anti-LMB-100 antibodies after 2 cycles of therapy. Intra-tumoral delivery of LMB-100 has been shown to induce immune cell infiltration in immune-competent mice, bearing murine malignant mesothelioma tumors. Combination with CTLA-4 blockage eradicates murine tumors by promoting anti-cancer immunity. Ipilimumab is a fully human anti CTLA-4 monoclonal antibody, that is approved for treatment of melanoma and in combination with nivolumab for many solid tumors. It is hypothesized that intra-tumoral delivery of anti-mesothelin immunotoxin LMB-100 in combination with ipilimumab will result in greater anti-tumor efficacy in patients with mesothelioma. Objective: To determine the safety and feasibility of intra-tumoral LMB-100 injection plus ipilimumab infusion in patients with mesothelioma To identify the recommended phase 2 dose (RP2D) of intratumorally administered LMB-100 + ipilimumab in patients with malignant mesothelioma Eligibility: Histologically confirmed pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection. Have locally accessible disease suitable for intra-tumor injection of LMB-100. This includes superficial or visceral lesions. Subjects must have received prior immune checkpoint therapy with anti-PD-1/PD-L1 inhibitors alone or in combination with anti-CTLA4 blocking antibodies, as well as platinum-based chemotherapy. Age >= 18 years. ECOG performance status of 0 or 1. Adequate organ and bone marrow function Subjects with clinically significant pericardial effusion are excluded Chemotherapy within 3 weeks or radiotherapy within 2 weeks prior to start of study therapy is prohibited. Subjects with active CNS metastasis are excluded Subjects with active autoimmune disease for which they have received systemic immunosuppressive medications during the previous 2 years (excluding daily glucocorticoid-replacement therapy for conditions such as adrenal or pituitary insufficiency) are excluded Subjects with active interstitial lung disease, or a history of pneumonitis or interstitial lung disease for which they had received glucocorticoids are excluded Design: This is an open-label, single center phase I dose escalation study of intratumorally administered LMB-concurrently with ipilimumab in subjects with malignant mesothelioma. Subjects will receive intratumorally administered LMB-100, beginning at dose level 1, in 21-day cycles. LMB-100 will be given on days 1 and 4 and ipilimumab 3 mg/kg given on day 2. Patients will receive 2 cycles of LMB-100 plus ipilimumab, followed by 2 cycles of ipilimumab alone Tumor biopsies will be performed prior to each administration of LMB-100, to evaluate changes in the tumor immune microenvironment Up to 12 evaluable subjects will be enrolled.

Tracking Information

NCT #
NCT04840615
Collaborators
Not Provided
Investigators
Principal Investigator: Raffit Hassan, M.D. National Cancer Institute (NCI)