Anti-Mesothelin Immunotoxin LMB-100 Followed by Pembrolizumab in Malignant Mesothelioma

NCT03644550 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 18013618-C-0136
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Treatment outcomes for people with pleural or peritoneal mesothelioma are often poor. The drug LMB-100 can attack and kill cancer cells. The drug pembrolizumab helps the immune system fight cancer. Together, these drugs might help people with these cancers. Objective: To test if pembrolizumab given after LMB-100 shrinks tumors in people with pleural or peritoneal mesothelioma. Eligibility: People ages 18 and older with pleural or peritoneal mesothelioma that has not responded to platinum-based therapy Design: Participants will be screened with: Tumor sample. Participants will have a biopsy if one is needed. Medical history Physical exam Blood, heart, and urine tests X-rays and scans: Participants will lie on a table. A machine will take pictures of the body. Participants will receive LMB-100 by intravenous (IV) on days 1, 3, and 5 of two 21-day cycles. They will be observed for up to 2 hours after each infusion. They will receive drugs like Benadryl, Tylenol, and Zantac to help with side effects. Starting with the 3rd cycle, participants will receive pembrolizumab by IV on day 1 of each 21-day cycle for up to 2 years. Participants will have blood and urine tests, heart tests, and chest x-rays at least once per cycle. They will have scans every 6 weeks. Participants may opt to provide tumor biopsies before starting the first cycle, after 2 cycles of LMB-100, and after 2 cycles of pembrolizumab. Participants will a follow-up visit 4-6 weeks after their last drug dose of the study drug. This includes blood and heart tests and scans. They may then have scans every 6 weeks. Participants will be contacted once a year for follow-up.

Conditions

Mesothelioma

Keywords

Checkpoint Inhibitor; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Objective Response (Partial Response + Complete Response)

  Number of participants who received at least 1 cycle of study therapy and who had their disease reevaluated that experienced a partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST criteria. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  Every 6 weeks until disease progression, an average of 3.1 months

Secondary Outcomes (5)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Date treatment consent signed to date off study, approximately 22 months and 29 days.

• Progression Free Survival (PFS)

  Time from start of treatment to time of progression (on or after pembrolizumab) or death, whichever occurs first, an average of 6.5 months

• Overall Survival (OS)

  Time between the first day of treatment to the day of death, an average of 17 months

• Duration of Overall Response (DOR)

  Time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, an average of 3.1 months

• Percentage of Participants With an Overall Response

  An average of 3.1 months.

Study Arms (1)

1/LMB- 100+pembrolizumab

EXPERIMENTAL

LMB-100 administered in cycles 1 and 2 + pembrolizumab administered in subsequent cycles. LMB-100 140mcg/kg Intravenous infusion (IVI), Days 1, 3, 5 in cycles 1, 2. Pembrolizumab 200mg IVI, every (Q) subsequent cycle on Day 1.

Drug: LMB-100; Biological: Pembrolizumab

Interventions

LMB-100 DRUG

Given intravenous (IV) at recommended phase 2 dose (RP2D) on days 1, 3 and 5 of two (2) 21 day cycles.

1/LMB- 100+pembrolizumab

Pembrolizumab BIOLOGICAL

Given intravenous (IV) at approved dose on day 1 of each 21 day cycle, starting with cycle 3, for up to 2 years with the option of a second course for patients meeting criteria.

Also known as: Keytruda

1/LMB- 100+pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply.
• Male and female participants who are at least 18 years of age on the day of signing the informed consent will be enrolled in the study.
• Subjects must have histologically confirmed diagnosis of:
• Cohort 1: Histologically confirmed epithelial or biphasic pleural mesothelioma (with \<50% sarcomatoid component) not amenable to potentially curative surgical resection. The diagnosis will be confirmed by the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI). OR
• Cohort 2: Histologically confirmed epithelial or biphasic peritoneal mesothelioma (with \<50% sarcomatoid component) not amenable to potentially curative surgical resection. The diagnosis will be confirmed by the Laboratory of Pathology, CCR, NCI.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Subjects must have at least one prior chemotherapy regimen that includes pemetrexed and cisplatin or carboplatin.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Evaluation of ECOG is to be performed within 7 days prior to start of study therapy.
• Have adequate organ and marrow function as defined below:
• Hematological- hemoglobin: \>= 9 g/dL or \>= 5.6 mmol/L(a)
• Hematological- absolute neutrophil count: \>= 1,500/mcL
• Hematological- platelets: \>= 100,000/mcL
• Hepatic- total bilirubin: less than or equal to 2.5 X institutional upper limit of normal (ULN) OR direct bilirubin less than or equal to ULN for participants with total bilirubin levels \>1.5 X ULN

You may not qualify if:

• \- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (\>= Grade 3) to pembrolizumab, LMB-100 and/or any of their excipients.
• Subjects who have received prior therapy with LMB-100, an anti-PD-1, anti-PD-L1, or anti-programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., Cytotoxic T-lymphocyte antigen 4 (CTLA-4), OX-40, tumor necrosis factor receptor superfamily member 9 (CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to start of study therapy.
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• Has had a prior pneumonectomy
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist(R)) are live attenuated vaccines and are not allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to start of study therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to start of study therapy (see Appendix B). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.

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; pembrolizumab

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

hassanr@mail.nih.gov

240-760-6232

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 23, 2018
• Study Start: December 4, 2018
• Primary Completion: August 5, 2020
• Study Completion: November 2, 2020
• Last Updated: December 2, 2021
• Results First Posted: December 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)