LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
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|ClinicalTrials.gov Identifier: NCT04027946|
Recruitment Status : Recruiting
First Posted : July 22, 2019
Last Update Posted : March 29, 2021
Over 230,000 new lung cancer cases are diagnosed every year in the U.S. About 80% of lung cancers are 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.
To find out if LMB-100 followed by pembrolizumab can help tumors to shrink in people with NSCLC.
People ages 18 and older with NSCLC that has not responded to standard therapies
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
- CT and PET scans: They will like 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.
|Condition or disease||Intervention/treatment||Phase|
|Lung Cancer Non Small Cell Lung Cancer Adenocarcinoma of Lung||Drug: LMB-100 Drug: pembrolizumab Diagnostic Test: Mesothelin Expression Diagnostic Test: TrueSight Oncology 500||Phase 2|
- Mesothelin is expressed in approximately half of all lung adenocarcinomas.
- LMB-100 has demonstrated anti-tumor efficacy against several mesothelin expressing tumor models including non-small cell lung cancer (NSCLC).- Programmed death ligand 1 (PD-1) is an Ig superfamily member related to CD28 and CTLA-4 that has been shown to negatively regulate antigen receptor signaling upon engagement of its ligands.
- Pembrolizumab, an IgG4 monoclonal antagonist antibody to PD-1, is FDA approved in the frontline for advanced non-squamous NSCLC as a single agent with high PD-L1 expression [tumor proportion score (TPS) >=50%] or in combination with platinum-based doublet chemotherapy (PD-L1 unselected). It also approved in the second-line for high PDL1 expressing tumors (TPS >=1%).
- Combination treatment with LMB-100 plus pembrolizumab results in greater anti-tumor efficacy in murine lung cancer model.
-To determine the objective response rate of LMB-100 followed by pembrolizumab in the treatment of subjects with mesothelin-expressing non-squamous non-small cell lung cancer (NSCLC) previously treated with immune checkpoint inhibitors.
- Histologically confirmed locally advanced or metastatic non-squamous, non-small cell lung cancer lacking an EGFR sensitizing mutation, ALK or ROS1 gene rearrangement and not amenable to potentially curative surgical resection or chemoradiation.
- Tumor mesothelin expression of at least 25% of tumor cells as determined by the Laboratory of Pathology at the NCI.
- Subjects must have at least progressed after one prior platinum-based doublet chemotherapy AND standard immune checkpoint inhibitor (ICI) with either frontline single-agent pembrolizumab, or in combination with platinum-based doublet chemotherapy, or second-line single-agent nivolumab, pembrolizumab, or atezolizumab.
- Age >= 18 years.
- This is an open-label, single center phase II study of LMB-100 followed by pembrolizumab in subjects with mesothelin expressing NSCLC who have progressed on standard therapies
- Subjects will receive LMB-100 at the single agent MTD (140mg/kg) on days 1, 3 and 5 of a 21-day cycle for up to 2 cycles and pembrolizumab 200 mg on day 1 of cycle 3 of a 21- day cycle (or cycle 2 if disease progression is observed after 1 cycle) onwards until disease progression (on or after pembrolizumab) or intolerable toxicity for a maximum of 2 years (unless second course initiated).
- The total accrual ceiling for the screening will be set at 100 total patients in order to treat 23 subjects.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC)|
|Actual Study Start Date :||September 11, 2019|
|Estimated Primary Completion Date :||April 30, 2021|
|Estimated Study Completion Date :||March 31, 2022|
Experimental: Arm 1
LMB-100 administered in cycles 1 and 2. Pembrolizumab administered in subsequent cycles
Patients will receive LMB-100 on days 1, 3 and 5 of a 21 day cycle for up to 2 cycles.
Patients will receive pembrolizumab on day 1 of each subsequent 21 day cycle.
Diagnostic Test: Mesothelin Expression
Testing for mesothelin expression performed at screening
Diagnostic Test: TrueSight Oncology 500
Testing for ROS1, ALK and EGFR variations performed at screening.
- Objective response rate [ Time Frame: Every 6 weeks until progression for up to 2 years ]Response will be evaluated per RECIST 1.1 criteria
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04027946
|Contact: Maria G Agra, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Azam Ghafoor, M.D.||National Cancer Institute (NCI)|