LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Adenocarcinoma of LungNon-Small Cell Lung CancerLung Cancer
- Interventions
- Diagnostic Test: Mesothelin ExpressionDiagnostic Test: TrueSight Oncology 500
- Registration Number
- NCT04027946
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
- Detailed Description
Background:
* 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 cluster of differentiation (CD28) and cluster of differentiation 152 (CTLA-4) that has been shown to negatively regulate antigen receptor signaling upon engagement of its ligands.
* Pembrolizumab, an immunoglobulin G4 (IgG4) monoclonal antagonist antibody to PD-1, is Food and Drug Administration (FDA) approved in the frontline for advanced non-squamous NSCLC as a single agent with high programmed death-ligand 1 (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.
Objectives:
-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.
Eligibility:
* Histologically confirmed locally advanced or metastatic non-squamous, non-small cell lung cancer lacking an EGFR sensitizing mutation, anaplastic lymphoma kinase (ALK) or ROS oncogene 1 (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.
Design:
* 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 maximum tolerated dose (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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Mesothelin Expressing Non-Small Cell Lung Cancer Participants Mesothelin Expression LMB-100 + Pembrolizumab Mesothelin Expressing Non-Small Cell Lung Cancer Participants LMB-100 LMB-100 + Pembrolizumab Mesothelin Expressing Non-Small Cell Lung Cancer Participants pembrolizumab LMB-100 + Pembrolizumab Mesothelin Expressing Non-Small Cell Lung Cancer Participants TrueSight Oncology 500 LMB-100 + Pembrolizumab
- Primary Outcome Measures
Name Time Method Proportion of Participants With Partial Response or Complete Response Reported With an 95% Confidence Interval End of treatment, an average of 83 days. 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.
Proportion of Participants With Partial Response or Complete Response Reported With an 80% Confidence Interval End of treatment, an average of 83 days. 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.
- Secondary Outcome Measures
Name Time Method Overall Survival Time from the start of treatment to death from any cause, a median of 22.9 months Overall survival is defined as the duration of time from start of treatment to death from any cause.
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. Progression free survival (PFS) is defined as the duration of 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.
Proportion of Participants With Grade 3 and Grade 4 Adverse Events Possibly, Probably, and Definitely Related to Pembrolizumab Date treatment consent signed to date off study, approximately 48.7 months Adverse events were evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 3 is severe. Grade 4 is life-threatening.
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. Response was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Number of Participants Who Are Treated Who Are Unable to Tolerate the Treatment Other Than Development of Adverse Events Date treatment consent signed to date off study, approximately 48.7 months Participants who are treated who are unable to tolerate the treatment other than development of adverse events
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. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
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 Adverse events were evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 3 is severe. Grade 4 is life-threatening.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States