The FDA recently approved Keytruda (pembrolizumab) for mesothelioma on a limited basis. Many experts are investigating how to enhance this drug and others like it.
A recent clinical trial may have stumbled upon a safe and effective option.
LMB-100 is a drug that targets mesothelin, which is a cancerous protein expressed on mesothelioma cells. The drug was the focus of a recent Phase 1 clinical study involving 21 mesothelioma patients. The National Cancer Institute, led by specialist Dr. Raffit Hassan, conducted the trial.
The study is not noteworthy due to the 21 patients receiving LMB-100, but rather for what happened to 10 of them afterward.
Ten patients received immunotherapy within one month after the anti-mesothelin therapy. Nine received pembrolizumab and one received nivolumab (known by its brand name “Opdivo”).
The results inspired the National Cancer Institute to conduct a clinical trial involving LMB-100 plus pembrolizumab. The trial is recruiting now — looking for 38 participants — and you could enroll. If interested, email our patient advocate and registered nurse Karen Ritter at firstname.lastname@example.org.
How LMB-100 and Immunotherapy Work Together to Fight Mesothelioma
The benefit of LMB-100 is that it doesn’t target a protein of necessity. Mesothelin is found on extraneous tissue, explicitly the tissue in the pleura and peritoneum, which is where mesothelioma forms. Mesothelin isn’t found on any vital organs, so the risk of toxicity from LMB-100 is low.
“It is really hard to find tumor antigens that can be targeted,” Dr. Hassan previously said of LMB-100, “but the fact that (mesothelin) is not expressed on an important organ makes it a good target for antibody-based therapies.”
LMB-100’s first objective is to bind to mesothelin on mesothelioma tumors. The drug then delivers a toxin into the diseased cells, which eventually undergo cell death.
However, mesothelioma is a stubborn, fast-spreading cancer. It duplicates and grows quickly, resulting in tiny microscopic tumors that move far from the point of origin. LMB-100 may bind to and attack one tumor, but it might not work fast enough to control the disease.
Immunotherapy for mesothelioma can help speed up the anti-tumor response.
Pembrolizumab is a checkpoint inhibitor that blocks the relationship between PD-1 and PD-L1. The former is a protein on the body’s T-cells, which respond to and attack diseased cells and viruses. PD-L1 is a protein sometimes expressed on mesothelioma cells.
When these two proteins bind, the T-cells ignore the mesothelioma cells. Pembrolizumab blocks the binding and helps T-cells to attack mesothelioma cells.
Pembrolizumab has shown extraordinary promise for mesothelioma patients with high PD-L1 levels. The FDA recently approved the Keytruda brand of this drug for pleural mesothelioma with high expressions of this protein.
Below is a video featuring Dr. Hassan. He explains how these immunotherapy drugs work against mesothelioma.
Dr. Hassan is part of multiple studies using LMB-100 for mesothelioma and other mesothelin cancers.
Tumor Response From LMB-100 and Immunotherapy
The National Cancer Institute team discovered that LMB-100 causes an inflammatory response in the tumor location. The body’s T-cells naturally respond to the inflammation, which puts many of these cancer-fighting cells near the tumors.
With the immunotherapy drug’s assistance, the T-cells can identify mesothelioma cells as dangerous. The immune system’s army is ready to help LMB-100 fight this cancer.
The median survival for all 10 patients was 11.9 months. However, half of them didn’t have high levels of PD-L1 expression. Immunotherapy drugs like pembrolizumab are best for patients with a high level of this protein.
Of the five with high PD-L1 levels, four (80%) experienced a tumor response. Three had a “partial response,” which means their disease shrank but was not entirely defeated. One patient had a complete response, which means the treatment eliminated all signs of disease.
The four patients’ average survival time, as of this publication, is 28.3 months:
- Two patients are still alive at 39 months and 32.6 months since the start of LMB-100 treatment.
- The other two patients survived for 27.7 months and 13.8 months.
For context, the expected survival time for most mesothelioma patients is between 9 and 18 months. An abnormally hopeful prognosis usually doesn’t exceed two years.
Sources & Author
- Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti–PD-1 antibody in patients with mesothelioma and mouse tumor models. Science Translational Medicine. Retrieved from: https://stm.sciencemag.org/content/12/550/eaaz7252. Accessed: 07/07/2020.
- Mesothelin-Targeted Immunotoxin LMB-100 in People With Malignant Mesothelioma. Clinicaltrials.gov. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT02798536. Accessed: 07/07/2020.
- Anti-Mesothelin Immunotoxin LMB-100 Followed by Pembrolizumab in Malignant Mesothelioma. U.S. National Library of Medicine. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03644550. Accessed: 8/26/18.
- Dr. Hassan on Immunotherapy in Malignant Pleural Mesothelioma. OncLiveTV. Retrieved from: https://www.youtube.com/watch?v=VxUupZC3UrI&feature=youtu.be. Accessed: 8/27/18.
Sources & Author