Author: Maja Belamaric
A new worldwide clinical trial for mesothelioma is now open for enrollment
The “handshake” between the tumor and T cell prevents a T cell immune attack against mesothelioma. Disrupting the “handshake” holds the key to an immune response against this cancer. This Phase 3 immunotherapy clinical trial for mesothelioma tests a drug made to do exactly that and is now available to patients in the United States and across the world.
A new phase 3 clinical trial testing the efficacy of dual checkpoint inhibitor immunotherapy in combination with chemotherapy is now available to patients in the United States as well as around the world. The official name for the study is MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma and the shortened name is eVOLVE-Meso.
This AstraZeneca study tests a single immunotherapy agent called volrustomig in combination with standard chemotherapy against either standard of care chemotherapy alone or immunotherapy alone. The study builds on the recent FDA-approval of immunotherapy for mesothelioma which saw two agents, nivolumab (Opdivo) and ipilimumab (Yervoy), activate the immune system against cancer cells by binding to two receptors located on the T cell: the PD-1 and the CTLA-4. Single agent volrustomig targets the same two proteins, but the study also adds standard chemotherapy to its protocol.
How to inquire about enrollment?
The clinical trial is widely available at centers across the United States. A patient should contact their treating physician to discuss enrollment. Locations where the Evolve-Meso clinical trial is available are listed here: https://clinicaltrials.gov/study/NCT06097728#contacts-and-locations.
How does immunotherapy work to kill mesothelioma cells?
To understand how immunotherapy treatment works, we must first understand why the immune system tends to stay inactive against mesothelioma cells. Both the T cell and other cells, including tumors, express proteins. When certain proteins on the T cell bind to their counterparts on a healthy cell, this communicates to the T cell to not attack the healthy cell. This is an important preservation mechanism that prevents autoimmune reactions. So when the tumor’s proteins bind to the ones on the T cell, they tell the immune system not to attack which allows the cancer to proliferate. Immunotherapy medications act as a decoy binding protein that binds to either the T cell or the tumor cell, disrupting their ability to bind with one another.
In the top part of this image, the T cell and the tumor cell connect causing no immune response against the tumor. In the bottom part of the image, the immunotherapy drugs connect to the expressed proteins on either the T cell or tumor thus inhibiting the connection between the two which in turn creates an immune reaction against the tumor. This is the basis of checkpoint inhibitor immunotherapy.
Immunotherapy + Chemotherapy: what is the rationale?
A common and valid question about combining chemotherapy with immunotherapy is: are we just throwing the kitchen sink at mesothelioma to see what sticks?
The answer is no.
There are, in fact, scientific reasons that would suggest that combining these two methods would lead to better results than administering them one at a time. Reason number one can be found in the answer to the question “why does the immune system not recognize mesothelioma as a foreign entity worth attacking from the beginning?” The answer is that mesothelioma cells’ receptors mimic those on the surface of healthy cells and they use the brakes built into the immune system to their advantage. But when chemotherapy is used to kill the cancer, the by-product of those dead cancer cells is seen as a foreign body by the immune system. So, adding chemotherapy to an immunotherapy regimen is one way to maximize the anti-tumor activity of both agents.
Timeline of FDA-approvals for mesothelioma
2004: Chemotherapy (Alimta/cisplatin)
2022: Immunotherapy (nivolumab / ipilimumab)
2024: Immunotherapy + chemotherapy for advanced mesothelioma (pembrolizumab also known by the brand name Keytruda, which is an anti-PD-1 agent, plus standard chemotherapy)
What is the difference between volrustomig and other immunotherapy agents used against mesothelioma
The volrustomig study is different from the 2024 immunotherapy (Keytruda) plus chemotherapy combination approval because volrustomig singularly binds to both the PD-1 and CTLA-4 receptors. Immunotherapy drugs targeting only the PD-1 or PDL1 receptors have shown to not be as effective as those also targeting the CTLA-4 receptor.
These two proteins, also known as checkpoint inhibitors, are located on the T cell. There, they play a crucial role in signaling to the immune system whether to attack the cancer cells or not. Without immunotherapy treatment, the tumor receptors (PD-L1 and CD80) bind to the reciprocal T cell receptors, signaling to the immune system not to attack the tumor. With immunotherapy that binds to them instead, the “handshake” between the tumor and the T cell is disrupted letting the immune system to attack the tumor.
Why should a patient consider participation in this study?
Mesothelioma patients have limited options for treatment available to them while the cancer is aggressive and moves fast. This study is an opportunity to try the combination of chemotherapy plus immunotherapy to potentially reap the most benefits.
What are the risks?
As with any study and/or treatment, one risk is that the treatment won’t work. With mesothelioma, this is a significant risk because the disease is quick and aggressive. However, over time, survival for mesothelioma patients has increased at least in part due to advancements in treatment options, and this study is one such option. Being a Phase 3 clinical trial, the drugs it uses have already been extensively studied for safety, but it is important to note that undergoing any type of immunotherapy can cause unintended immune reactions some of which can be life threatening. Speaking with the treating physician about potential risks and benefits is an important part of enrolling into a clinical trial.
What other treatments are in the works for mesothelioma?
Two other significant studies have been released in the last two years, both holding promise with regards to further treatment approvals. Both studies showed an improvement in survival in the most aggressive type of mesothelioma called the sarcomatoid subtype.
One of these studies combined Alimta/cisplatin (chemotherapy) with atezolizumab (immunotherapy) and also with bevacizumab (a VEGF inhibitor agent that limits vascular development leading to the tumor).
The other study, called ATOMIC, was successful in improving survival in the sarcomatoid and biphasic mesothelioma subtypes (most aggressive) by depriving the cancer cells of arginine, which is generally widely present in the most aggressive mesotheliomas.
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New episode of Meet the Mesothelioma Experts About Financial Compensation for Mesothelioma
Last week, the Mesothelioma Applied Research Foundation released a new episode of its Meet the Mesothelioma Experts: Legal Edition series discussing financial compensation issues for mesothelioma patients. Featured guest of the program was Joseph Belluck, partner with the Belluck & Fox firm, who was interviewed by the organization’s board of directors’ member, Cheryl Bruner. Mr. Belluck answered a number of questions of interest to those who have just had a mesothelioma diagnosis and their families.
Acting with Urgency
One of the take-home messages is that while a mesothelioma diagnosis requires medical urgency and treatment, so does the legal process. This is due to a number of issues, the statute of limitations being one, but not the only one. As Mr. Belluck states in this program, it is important to file a lawsuit as soon as realistically possible in order to get a place in line, even if later adjustments are necessary. An experienced law firm will know enough information about a case very quickly and will be able to proceed with expedience.
“Usually, right after contact, we file the case, we start working on the bankruptcy trust claims and also starting to work on the lawsuit, which we do in tandem. Typically, the first settlements will come in about 45 – 60 days and the whole case will be completed within 12 months,” said Mr. Belluck in the program.
Mr. Belluck adds that whether a patient chooses to hire his firm or another firm, he still encourages them to make sure to do so quickly for the reasons outlined above.
Watch the video:
00:00 Introduction
1:11 Why Belluck & Fox chooses to sponsor the Meso Foundation and how their mission resonates
6:15 How Belluck & Fox works within the meso community
7:47 Next steps in the legal process after diagnosis
11:05 Litigation timeline after choosing a law firm
14:01 How much time and effort is anticipated to dedicate to litigation
16:14 Options for taking legal action
21:58 Timeline of settlement funds
28:05 How much of a settlement does a patient/family receive
35:37 Advice for future clients in deciding legal action
Compensation Programs for Mesothelioma Patients and their Families
There are several main compensation programs that are typically available to mesothelioma patients. They include simple programs like health insurance, private disability insurance, social security disability benefits, and workers compensation if the person is still employed. Additionally, veterans’ benefits are available for people who served in the military and have a service connection to asbestos exposure. Mesothelioma bankruptcy trusts are another avenue to pursue for compensation. There are about 40-50 individual funds that have been set up by companies that made asbestos products and went into bankruptcy. As part of their bankruptcy reorganization, they set up a fund for their product. And the last option available is to file a lawsuit individually, not a class action, against the companies that made asbestos products that the patient was exposed to.
Mr. Belluck and his law firm offer free consultations by submitting a quick form on the firm’s website at www.belluckfox.com.
Mesothelioma Treatment News: Delivering therapies directly into the pleural space
In a new article published in the medical journal The Lancet (Leveraging the pleural space for anticancer therapies in pleural mesothelioma by Blythe at al., 2024), authors make an argument for renewed focus toward therapies that can be delivered directly into the intrapleural space.
The benefit of such therapies is that by targeting the tumor directly, doctors are able to use higher doses of medication for increased likelihood of success while limiting toxicity to the patient.
Pleural mesothelioma is a cancer of the lining that surrounds the lung, which is called the pleura. So far, most attention has been devoted toward finding systemic treatments that work – a feat that has proven to be quite challenging. Systemic treatments are treatments such as chemotherapy or immunotherapy, which are administered through a vein, that travel throughout the entire body to kill the cancer cells wherever they may be. These treatments are currently the standard of care, but many patients’ tumors still don’t respond to them well. Because most patients’ cancer is quite advanced at diagnosis, this approach is often the only option anyway.
However, some patients receive a very early diagnosis either incidentally, meaning they underwent a surgical procedure for a different issue when mesothelioma was found; or because they presented with fluid buildup in the pleural space (called a pleural effusion) that prompted further testing. Recent staging studies suggest that this population of patients is significantly larger than previously thought and might include anywhere between 15% to 40% of diagnoses. For such patients, benefits of systemic therapies are unclear because studies that led to the FDA approval of chemotherapy and immunotherapy predominantly included unresectable (non-surgical candidates) stage 3 and 4 patients. Typically, early-stage patients are either offered surgery, or watchful waiting. But in the past year, this approach has been further complicated by a somewhat controversial surgical study called MARS 2 which showed limited benefits of surgery in the management of mesothelioma. Therefore, the expectation is that the number of early-stage patients who receive no immediate treatment will increase.
For this reason, the authors suggest that development of studies to test the effectiveness of localized intrapleural treatment is important and feasible and can be performed during the wait period between diagnosis and standard treatment, called window of opportunity.
In its early stages, mesothelioma’s only symptom might be a pleural effusion, either symptomatic or not. If symptomatic, once the effusion is drained, the patient feels better. But as long as mesothelioma is present on the pleura, it is rare for the fluid to stop building up. Currently, there are two ways to manage this problem:
- With a procedure called pleurodesis. The purpose of the procedure is to close the space in the pleura where fluid accumulates. This procedure makes the pleural space mostly inaccessible.
- By inserting a drain catheter into the pleural space to drain the fluid as it builds up, thus leaving the pleural space accessible.
Critically, administering intrapleural therapy will require access to the pleura, so the initial course of action for palliation of the pleural fluid will need to be reviewed and will require consensus among providers. It is important to note that a previous pleurodesis might not necessarily be a disqualifying factor as long as pleural pockets of air/fluid are still present.
This article is a summary of a research study and does not constitute medical advice.
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