What the 2025 iMig Conference Revealed About the Future of Mesothelioma Treatment
The biannual meeting of the International Mesothelioma Interest Group (iMig) brought forward a mix of clinical insights, scientific advances, and ongoing debates that continue to shape the care of patients with mesothelioma. Several themes rose to the forefront, from how surgery fits into modern treatment strategies to emerging targets like the Hippo pathway and the evolution of systemic therapies.
Surgery and the Legacy of the MARS2 Trial
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A large portion of discussion centered on surgery for pleural mesothelioma, particularly in light of the MARS2 trial from the United Kingdom. This multicenter study enrolled patients who received two cycles of chemotherapy and who were then randomized to continue chemotherapy alone or to receive surgery followed by more chemotherapy. The trial found no survival advantage from adding surgery, upending the surgical and medical oncologists’ understanding of best practices. The results have sparked an active debate about the study’s methods and validity of its findings.
In fact, presenters noted that experienced mesothelioma surgeons view the trial as limited in ways that may not reflect real world practice. Key concerns include the overall mortality seen in the surgical arm of the study with specific questions surrounding patient selection. High volume centers in the United States continue to see a role for surgery as part of a multimodality plan, provided the procedures are performed at centers managing more than 25 cases per year. The consensus in these discussions held that while surgery for mesothelioma is not curative and an R0 resection is not achievable, operations are offered as one component in a broader strategy that combines systemic therapy before or after surgery, with the understanding that recurrence is expected.
Speakers emphasized a practical point. Patients want options that give them a chance to live beyond five years. Current systemic therapies offer median survival in the range of one and a half to two years, so refining surgical approaches and pairing them with modern systemic treatments remains important. Clinical trials exploring immunotherapy in the neoadjuvant or adjuvant setting were highlighted as an active and promising direction.
Targeting the Hippo Pathway with TEAD Inhibitors
New therapeutic targets also captured attention. Dysregulation of the Hippo pathway is seen in about 60% of mesothelioma cases, making it an appealing area for drug development. Currently, several agents are in development or seeking regulatory approvals, including Vivace VT3989, a TEAD palmitoylation inhibitor being tested in advanced refractory solid tumors, and IAG933, which works by binding the TEAD coil site and displacing YAP and TAZ.
The Hippo pathway is a signaling system that helps keep organ size in check by guiding how cells grow, die, and mature. When this pathway is switched on, it keeps the proteins YAP and TAZ out of the nucleus, which slows cell growth. When the pathway is switched off, YAP and TAZ enter the nucleus and activate genes that support cell growth, division, and survival.
In addition, preclinical work continues to build the case for combining TEAD inhibition with immunotherapy. Research presented at the meeting, including findings discussed in a recent JTO publication, suggests that blocking the YAP TEAD interaction may help T cells penetrate the tumor environment more effectively. Early data indicate that some mesotheliomas respond to TEAD inhibitors, though baseline Hippo pathway abnormalities alone are not enough to predict which patients will benefit.
Current Systemic Therapies and What Lies Ahead
The meeting also reviewed the status of approved treatments and the next wave of clinical trials. In the second line, single agent immunotherapy continues to play a role. In pre-treated relapsed patients, nivolumab has shown superiority to placebo in progression-free survival with a modest improvement in overall survival. Also in second line, pembrolizumab performs similarly to agents like gemcitabine or vinorelbine, with progression-free survival around two and a half months and median survival just over ten months.
Several major trials represent the push toward more effective combinations.
- BEAT meso tested a regimen that adds bevacizumab and atezolizumab to standard chemotherapy.
- IND 227 compared chemotherapy alone to chemotherapy with pembrolizumab and has shown particular benefit in non-epithelioid tumors such as sarcomatoid and biphasic subtypes. This trial was the foundation for the latest FDA-approval of Merck’s Keytruda (pembrolizumab) in combination with chemotherapy for patients with sarcomatoid and biphasic tumors.
- MIST 4 evaluated atezolizumab and bevacizumab in patients who previously received platinum-based chemotherapy.
- RAMES has studied gemcitabine with either placebo or ramucirumab.
- Trials of anetumab ravtansine, both as a second line therapy compared against vinorelbine and in combination with pembrolizumab, continue to explore antibody drug conjugates as part of the treatment landscape.
Progress for Sarcomatoid and Biphasic Mesotheliomas
Sarcomatoid and predominantly sarcomatoid mesothelioma tumors have traditionally been known as extremely aggressive and non-responsive to most treatment options. However, in recent years, we have seen significant benefits in survival for patients with those subtypes of mesotheliomas thanks in large part to immunotherapy. Over and over, clinical trials have demonstrated that, for those patients, immunotherapy works better than anything else. Unfortunately, immunotherapy’s side effects can be unpredictable, and when severe, therapy must be discontinued. For those patients, a new option may be on the horizon.
- ATOMIC-meso trial concluded recently that in nonepitheliod pleural mesothelioma, adding pegargiminase to the chemotherapy treatment increased overall survival by 1.6 months and quadrupled survival at 36 months when compared to the arm that only received chemotherapy. Pegargiminase works by depleting arginine from tumors that already lack the ability to make this compound themselves. Without arginine, tumor cells weaken and can’t proliferate as well.
Looking Ahead
Across sessions, the tone was both realistic and forward-looking. Experts acknowledged the challenges that remain but pointed to meaningful steps being taken through surgical refinement, deeper understanding of the tumor and its microenvironment, targeted pathways like Hippo, and more effective systemic combinations. The meeting reinforced that mesothelioma care continues to evolve through collaboration, high quality trials, and the willingness to question assumptions while pushing for better outcomes for patients.
About Belluck Law, LLP
Belluck Law, LLP is a proud top sponsor of the 2025 meeting of the International Mesothelioma Interest Group (iMig). The nationally recognized firm has a long history of advocating for individuals and families impacted by asbestos exposure and mesothelioma.
With offices throughout New York State, including New York City, Albany, Rochester, Woodstock, and Gloversville, as well as in Maine, Massachusetts, and New Jersey, Belluck Law has secured over $1 billion in verdicts and settlements for its clients. Its attorneys consistently earn recognition from Best Lawyers, Super Lawyers, Martindale-Hubbell, and other respected legal evaluators.
In September 2025, the firm secured two major victories: an $83 million verdict for a client exposed to asbestos through clay products, and a $12.25 million verdict for another client exposed while living near a talc mine.
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