What Experts Revealed at iMig 2025 About the Next Wave of Mesothelioma Therapies

• Maja Belamaric
• Featured News
• December 3, 2025

The 2025 gathering of the International Mesothelioma Interest Group (iMig) offered a powerful snapshot of where treatment for mesothelioma is heading, with a mix of clinical debate, scientific breakthroughs, and evolving therapeutic strategies. Several recurring themes emerged, notably around the role of surgery, advances in targeted therapies, and the expanding use of systemic treatments.

Surgery Under Scrutiny, but Still an Option in the United States

One of the central conversations revolved around the findings of the MARS2 trial, a UK-based multicenter study that randomized pleural mesothelioma patients (after two cycles of chemo) to either continue chemotherapy alone or undergo surgery followed by further chemo. The trial concluded that surgery provided no clear survival benefit.

These results shook long-held assumptions in the field and stimulated a strong re-evaluation of when surgery should be used. Experienced surgeons at the conference argued that the trial may not reflect optimal, real-world surgical practice citing concerns about patient selection and higher mortality in the surgical group.

Still, some high-volume mesothelioma centers (especially those handling 25+ cases per year) maintain that surgery can remain part of a broader multimodal treatment plan. In other words: though surgery may not cure, it could help extend life when combined with modern systemic therapies performed at experienced centers.

Because current systemic treatments yield a median survival around 18–24 months, combining refined surgical strategies with systemic therapy remains a goal. Trials incorporating immunotherapy either before or after surgery were spotlighted as especially promising.

A New Target: The Hippo Pathway and TEAD Inhibitors

Beyond surgical debates, researchers pointed to new molecular avenues such as the dysregulated Hippo pathway, which is disrupted in roughly 60% of mesothelioma cases. This makes it an attractive target for drug development.

Agents like Vivace VT3989 (a TEAD palmitoylation inhibitor) and IAG933 (which interferes with TEAD-YAP/TAZ interactions) are currently under development or in regulatory review for advanced solid tumors, including mesothelioma.

Preclinical data presented at iMig suggest that combining TEAD inhibition with immunotherapy may enhance immune cell infiltration into tumors, potentially improving effectiveness. However, the presence of Hippo pathway abnormalities alone isn’t yet a reliable predictor of who benefits.

This line of research could open new doors for patients, especially those whose tumors aren’t well served by existing chemo or immunotherapy regimens.

Systemic Therapies

Attendees reviewed the current arsenal of systemic treatments and looked ahead to future combinations. For patients who relapse, single-agent immunotherapy remains an option: for example, nivolumab has demonstrated improved progression-free survival compared with placebo, though overall survival gains are modest.

Other agents, such as pembrolizumab, show response rates in relapsed disease similar to older chemo drugs like gemcitabine or vinorelbine.

More importantly, several clinical trials are now exploring combinations intended to improve outcomes. For instance:

• The BEAT‑meso trial is testing standard chemo plus a blend of an immunotherapy agent and a VEGF inhibitor.
• The IND 227 trial compared chemo alone to chemo plus pembrolizumab, revealing particular benefit for non-epithelioid subtypes such as sarcomatoid or biphasic mesothelioma.
• Other trials include MIST 4 trial (atezolizumab + bevacizumab after prior chemo), RAMES trial (gemcitabine with ramucirumab vs. placebo), and investigations of antibody-drug conjugates like anetumab ravtansine, either alone or combined with immunotherapy.

New Hope for Aggressive Subtypes: Sarcomatoid and Biphasic Mesothelioma

Patients with sarcomatoid or mostly sarcomatoid tumors have long faced grim prognoses, given that those subtypes respond poorly to standard treatments. Results from studies in recent years, though, have shown growing evidence that immunotherapy can meet a critical need here.

One particularly important development: in nonepithelioid pleural mesothelioma, the combination of chemotherapy with pegargiminase significantly improved outcomes in the ATOMIC‑meso trial. According to the data discussed, pegargiminase caused a modest increase in overall survival (about 1.6 months), but more strikingly, quadrupled 3-year survival compared to chemotherapy alone. The drug works by starving tumor cells of arginine, a nutrient certain mesothelioma cells can’t produce on their own, which weakens their growth ability.

While immune-based regimens remain powerful, they can also lead to unpredictable side effects; in such cases, pegargiminase represents a promising alternative or addition for individuals who may not tolerate immunotherapy or who are not candidates for immunotherapy.

What’s Next

Discussions at iMig underscored a balance between realism and optimism. On one hand, the field recognizes the many hurdles left to overcome as mesothelioma remains difficult to treat, and no single approach is a silver bullet. On the other, there is clear momentum toward better patient outcomes, built on improved surgical techniques, deeper biological understanding, novel drug targets, and smarter combination therapies.

The conference reaffirmed that the future of mesothelioma care likely lies in personalization: matching treatment strategies (surgery, chemo, immunotherapy, targeted agents) to tumor biology, disease subtype, and patient condition. With ongoing clinical trials and evolving research, there is growing hope that the standard of care will continue to shift giving patients more options and, ultimately, much more time.