Each new mesothelioma clinical trial places one more piece in the puzzle of mesothelioma treatment. But sometimes, a mesothelioma clinical trial will add a whole new dimension to the puzzle with new pieces waiting to be filled in. That’s what happened when scientists studied a new drug, LMB-100.
Recent trials of a lab-created protein called LMB-100 uncovered two facts about this potential mesothelioma immunotherapy treatment: it worked well for some patients but not at all for others. In those patients, researchers found, the drug stimulated an immune response that neutralized its benefits.
Scientists have used this new information to frame a new mesothelioma clinical trial that is now recruiting patients. The study will combine LMB-100 with SEL-110, a drug they hope will prevent the immune response that neutralizes LMB-100.
Mesothelioma Clinical Trial Uncovers Anti-Drug Antibodies
Inside each of our bodies is a complex universe. Millions of tiny particles perform specialized functions that control everything from blinking your eyelid to digesting the burger you had for lunch to protecting you from infection and disease.
As scientists develop better tools to peer into these systems, they have come to understand more about how our bodies function at a molecular level. This has led to potential breakthroughs in the treatment of mesothelioma and other cancers. Immunotherapy drugs direct the power of our immune systems against cancerous tumors.
But the human body is infinitely complex. So it’s not surprising that the promise of mesothelioma treatments that use our own biological systems has not been fully realized. Researchers have discovered that our immune systems sometimes react by developing anti-drug antibodies (ADAs).
That’s exactly what scientists found during more than one mesothelioma clinical trial of LMB-100, which could help mesothelioma patients as well as patients with pancreatic and other cancers. While some patients responded well and their tumors shrank, others developed ADAs to LMB-100.
Mesothelin and Mesothelioma
To better understand the new LMB-100 trial, it’s helpful to review the role of mesothelin in mesothelioma and other cancers. Mesothelin (abbreviated as MSLN) is a protein that helps form the mesothelium. The mesothelium are the thin tissues that form sacs around organs in our bodies. The pleura is the mesothelium around the lungs. The peritoneum is the sac that encases the organs of the abdomen. Mesothelioma is a rare cancer that most often forms in the pleura and can also start in or metastasize to the peritoneum.
There is more mesothelin protein in the cells of certain cancers than in normal cells. Mesothelin encourages tumors to form and metastasize to other parts of the body. Metastatic cancers tend to be even more deadly than the original tumors, so preventing the spread of cancerous cells is crucial to long-term survival for cancer patients. Mesothelin protein is also immunogenic, which means it can stimulate an immune response from your body.
Because of these factors, mesothelin is seen as a promising avenue for new mesothelioma immunotherapy research. A drug that reduces the production of mesothelin has the potential to keep a tumor from growing and metastasizing. That’s where LMB-100 comes in.
Mesothelioma Clinical Trial of LMB-100 with SEL-110
The full name of LMB-100 is anti-mesothelin cytolytic fusion protein LMB-100. The drug is made from a combination of elements including a binding segment of antibody. In the body, LMB-100 is drawn to cells with excess mesothelin, where it hinders the creation of mesothelin protein. LMB-100 also encourages apoptosis in tumor cells with excess mesothelin. Apoptosis is the programmed cell death cycle that normal cells follow and cancer cells avoid.
The National Cancer Institute (NCI) has two studies of LMB-100 underway. One is a mesothelioma clinical trial to determine a safe dose of the drug for mesothelioma patients. The other is looking at the response of patients with pancreatic cancer to LMB-100 in combination with another pancreatic cancer drug. In the course of clinical trials, researchers have determined that LMB-100 drug produced an ADA response in some patients.
The new study, clinical trial NCT03436732, is called Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma. The study is sponsored by NCI and administered out of the National Institutes of Health Clinical Center in Bethesda, Maryland. It is currently enrolling patients with pleural or peritoneal mesothelioma. Mesothelin is thought to be an especially important factor in the formation of peritoneal mesothelioma.
SEL-110 is a nanoparticle that prevents the immune system from attacking proteins like LMB-100 when the two are given at the same time. Participants in this mesothelioma clinical trial will receive SEL-110 at the same time as their first dose of LMB-100. Both cancer-fighting treatments are administered intravenously, usually through the arm.
The study will take place in 21-day cycles and patients can participate in up to four cycles. In each cycle, patients receive LMB-100 for a half hour and SEL-110 for an hour on day one. On days three and five, patients will receive LMB-100 alone.
This current mesothelioma clinical trial is a Phase 1 study. The purpose is primarily to determine the dose of LMB-100 and SEL-110 that patients can tolerate. The study will also help to determine whether SEL-110 prevents patients’ immune systems from forming antibodies to LMB-100. Every participant will receive the drugs; there are no placebos. The study aims to enroll 40 participants.
This study is only open to patients with advanced mesothelioma who have been unsuccessfully treated with a platinum-based chemotherapy drug (platins like cisplatin or carboplatin). The screening for this mesothelioma clinical trial will involve a medical examination, a blood test, a urine sample, and a PET scan. Mesothelioma patients will also need to provide researchers with a sample of their tumor tissue. The sample can come from a previous biopsy.
If you meet the criteria, this mesothelioma clinical trial could be an opportunity to test a promising new biotherapy. If you don’t qualify, there are many other clinical trials and new trials starting all the time. Mesothelioma Circle’s clinical trial tool can help you connect to a clinical trial that’s right for you.
Participating in a mesothelioma clinical trial is not without risk. You may experience negative side effects. The treatment may not work for you. But there are also major rewards. You may get early access to a promising new mesothelioma treatment before it is offered to the general public. And you advance the science of cancer treatment. The information from each mesothelioma clinical trial moves scientists one more step toward better mesothelioma treatments.