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

NCT03436732 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 18005718-C-0057
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mesothelioma

Keywords

Immunotoxin; Rapamycin; Targeted Therapy; Mesothelin

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg

  Here are the grade ≥3 adverse events at each dose level assessed by the Common Terminology Criteria in Adverse Events CTCAE v5.0. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is Severe or medically significant but not immediately life-threatening;hospitalization or prolongation of hospitalization indicated; disabling;limiting self care ADL (i.e., bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 is life-threatening consequences;urgent intervention indicated. Grade 5 is death related to adverse event.

  Day 85

• Maximum Tolerated Dose (MTD)

  MTD is defined as the highest tested dose of LMB-100 and SEL-110 at which no more than 1 of 6 subjects experience a dose limiting toxicity. A dose limiting toxicity is defined as any of the following: Grade 4 neutropenia for a minimum duration of 7 days. Grade 4 thrombocytopenia (≤25.0 x 10(9) cells/L), Grade 3 thrombocytopenia associated with bleeding episodes, and Grade 4 anemia. Grade ≥3 non-hematological toxicity with the exception of Alopecia (any grade), Grade 3 nausea and vomiting lasting \> 48 hours despite appropriate treatment, Grade 3 diarrhea lasting for ≤ 2 days with no fever or dehydration, and laboratory values of ≥ grade 3 that are judged not clinically significant by the investigator. Any other drug related toxicity considered significant enough to be qualified as a DLT in the opinion of the principal investigator. Inability to start cycle 2 within 3 weeks after completing cycle 1 due to drug-related adverse events.

  Day 21

Secondary Outcomes (3)

• Number of Participants With Partial Response or Complete Response (PR + CR)

  42 days

• Fraction of Participants With Detectable LMB-100 in Blood After Cycle 4

  Day 85

• Number of Participants With Serious and Non-Serious Adverse Events

  Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.

Study Arms (2)

1/Dose Escalation

EXPERIMENTAL

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

Drug: LMB-100; Drug: SEL-110

2/Dose Expansion

EXPERIMENTAL

Dose expansion - patients with mesothelioma treated with LMB-100+SEL-110 at recommended phase 2 dose (RP2D)

Drug: LMB-100; Drug: SEL-110

Interventions

LMB-100 DRUG

administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

1/Dose Escalation; 2/Dose Expansion

SEL-110 DRUG

administered on day 1 of each cycle for up to 4 cycles

1/Dose Escalation; 2/Dose Expansion

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed epithelial or biphasic pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a more than or equal to 50% sarcomatoid component will be excluded.
• The diagnosis will be confirmed by the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI).
• Archival sample or fresh biopsy or tumor effusion must be available for confirmation of diagnosis.
• 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.
• The last dose of previous therapy must have occurred at least 3 weeks prior to the start of study therapy. Palliative radiotherapy is allowed up to 2 weeks before the first LMB-100 infusion.
• Patients for whom no standard curative therapy exists
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of LMB-100 + SEL-110 in patients \<18 years of age, children are excluded from this study
• All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade less than or equal to 1, except alopecia (any grade) and Grade 2 peripheral neuropathy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Adequate hematological function: neutrophil count of more than or equal to 1.0 times 10(9) cells/L, platelet count of greater than or equal to 100,000/mcL, hemoglobin more than or equal to 9 g/dL
• Adequate liver function: Bilirubin less than or equal to 2.5 times the upper limit of normal (ULN) (excluding Gilbert's Syndrome, see below).
• Unconjugated hyperbilirubinemia noted on several occasions
• No evidence of hemolysis (normal hemoglobin, reticulocyte count, and lactate dehydrogenase (LDH))
• Normal liver function tests

You may not qualify if:

• Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases. History or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days.
• Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including significant pulmonary disease other than primary cancer, uncontrolled diabetes mellitus, and/or significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, uncontrolled arrhythmias, unstable angina, non-compensative congestive heart failure, or clinically significant pericardial effusion)
• Active or uncontrolled infections.
• Human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. HIV positive patients will be excluded due to a theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
• Patients with prior pneumonectomy
• Prior therapy with LMB-100
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
• Major surgery or significant traumatic injury greater than or equal to 28 days prior to the first LMB-100 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
• Dementia or altered mental status that would prohibit informed consent
• Live attenuated vaccinations 14 days prior to treatment
• Pregnant women are excluded from this study because it is unknown whether LMB-100 + SEL 100 has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LMB-100+SEL-110, breastfeeding should be discontinued if the mother is treated with LMB-100+SEL-110. These potential risks may also apply to other agents used in this study.
• Known hypersensitivity to any of the components of LMB-100 and/or SEL-110
• Presence of immunosuppressive conditions, including administration of any medications or treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs, or systemic corticosteroids (oral or injectable) during 3 months prior to enrollment.
• Inhaled and topical corticosteroids allowed.
• Known allergy to polyethylene glycol (PEG)ylated products.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mesothelioma

Interventions

LMB-100

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Results Point of Contact

• Title: Dr. Raffit Hassan
• Organization: National Cancer Institute

rh276q@nih.gov

240-760-6322

Study Officials

• Raffit Hassan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: February 19, 2018
• Study Start: February 28, 2018
• Primary Completion: April 30, 2019
• Study Completion: April 30, 2019
• Last Updated: November 22, 2019
• Results First Posted: November 22, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)