LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

NCT04027946 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 19012719-C-0127
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Over 230,000 new lung cancer cases are diagnosed every year in the United States (U.S.) About 80% of lung cancers are non- small cell lung cancer (NSCLC). Most people have a more advanced stage of the disease that doesn't respond well to standard treatment. Researchers want to see if a combination of drugs may be able to help. Objective: To find out if LMB-100 followed by pembrolizumab can help tumors to shrink in people with NSCLC. Eligibility: People ages 18 and older with NSCLC that has not responded to standard therapies Design: Participants will be screened with:

• Medical history
• Physical exam
• Tumor sample. If one is not available, they will have a biopsy.
• Assessments of ability to perform normal activities
• Lung function tests
• Blood, heart, and urine tests
• Computed tomography (CT) and positron emission tomography (PET). They will lie in a machine that takes pictures of the body. Participants will take LMB-100 in 21-day cycles for up to 2 cycles. They will take the drug by injection into an arm vein on days 1, 3, and 5 of each cycle. They will stay in the hospital 7-10 days each cycle. Then they will get pembrolizumab by injection into an arm vein every 3 weeks for up to 2 years. They may be able to take pembrolizumab an additional year if their cancer gets worse. Participants will have repeats of the screening tests throughout the study. About 30 days and 90 days after they stop treatment, participants will have follow-up visits. Then they will have visits every 6-12 weeks. They will be followed for the rest of their life through phone calls and emails.

Conditions

Lung Cancer; Non-Small Cell Lung Cancer; Adenocarcinoma of Lung

Keywords

Immunotherapy; Checkpoint Inhibitor; Monoclonal Antibody; Lung Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants With Partial Response or Complete Response Reported With an 80% Confidence Interval

  Participants with a partial response or complete response is reported with an 80% confidence interval. Response was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. 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.

  End of treatment, an average of 83 days.

• Proportion of Participants With Partial Response or Complete Response Reported With an 95% Confidence Interval

  Participants with a partial response or complete response is reported with an 95% confidence interval. Response was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. 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.

  End of treatment, an average of 83 days.

Secondary Outcomes (7)

• Overall Response (OR)

  From the start of the treatment until disease progression/recurrence (taking as reference for progressive disease), an median of 22.9 months.

• Number of Participants With a Response

  Beginning at the date a participant is noted to have at least a partial response (PR), an average of 2.7 months.

• Progression Free Survival (PFS)

  Time from start of treatment to time of progression (on or after pembrolizumab) or death, whichever occurs first, calculated from the on-study date using the Kaplan-Meier method, an average of 2.7 months.

• Overall Survival

  Time from the start of treatment to death from any cause, a median of 22.9 months

• Proportion of Participants With Grade 3 and Grade 4 Adverse Events Possibly, Probably, and Definitely Related to LMB-100

  Date treatment consent signed to date off study, approximately 48.7 months

Other Outcomes (1)

• 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 48.7 months

Study Arms (1)

Mesothelin Expressing Non-Small Cell Lung Cancer Participants

EXPERIMENTAL

LMB-100 + Pembrolizumab

Drug: LMB-100; Drug: pembrolizumab; Diagnostic Test: Mesothelin Expression; Diagnostic Test: TrueSight Oncology 500

Interventions

LMB-100 DRUG

Participants will receive LMB-100 on days 1, 3 and 5 of a 21-day cycle for up to 2 cycles.

Mesothelin Expressing Non-Small Cell Lung Cancer Participants

pembrolizumab DRUG

Participants will receive pembrolizumab on day 1 of each subsequent 21-day cycle.

Also known as: Keytruda

Mesothelin Expressing Non-Small Cell Lung Cancer Participants

Mesothelin Expression DIAGNOSTIC_TEST

Testing for mesothelin expression performed at screening

Mesothelin Expressing Non-Small Cell Lung Cancer Participants

TrueSight Oncology 500 DIAGNOSTIC_TEST

Testing for ROS oncogene 1 (ROS1) gene, anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) variations performed at screening.

Mesothelin Expressing Non-Small Cell Lung Cancer Participants

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 non-squamous non-small cell lung cancer not amenable to potentially curative treatments (surgical resection, definitive radiation therapy or a combined modality approach) or targeted agents to actionable epidermal growth factor receptor (EGFR) mutations or Anaplastic lymphoma kinase (ALK) or ROS oncogene 1 (ROS1) gene rearrangement and excluding neuroendocrine tumors. Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are allowed. The diagnosis must be confirmed by the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI). Mutation confirmation may be done by referring institutions or by one of the assays in the Protocol.
• Have provided archival tumor tissue sample or newly obtained fresh 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.
• Histologically confirmed 25% of tumor cells expressing mesothelin as determined by NCI Laboratory of Pathology. Determination can be made using archival tumor tissue or fresh biopsy.
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST). Lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Subjects must have received prior standard of care treatments for locally advanced or metastatic non-small cell lung cancer (NSCLC).
• Patients must be more than 3 weeks out of systemic treatments, such as chemotherapy.
• All acute toxic effects of any prior radiotherapy, chemotherapy, immunotherapy, 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 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:
• Patients must have normal organ and marrow function as defined below:
• hemoglobin greater than or equal to 9g/dL or 5.6 mmol/L
• absolute neutrophil count greater than or equal to 1,500mcL

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

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung

Interventions

LMB-100; pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Dr. Azam Ghafoor
• Organization: National Cancer Institute

azam.ghafoor@nih.gov

240-858-3289

Study Officials

• Azam Ghafoor, 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: July 19, 2019
• First Posted: July 22, 2019
• Study Start: September 11, 2019
• Primary Completion: June 17, 2020
• Study Completion: December 22, 2023
• Last Updated: April 16, 2024
• Results First Posted: July 18, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing Plan (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)