8 Mesothelioma Trials Compared: Results Side by Side

Eight major clinical trials have shaped how mesothelioma is treated in 2026. Two led to FDA approvals. One overturned decades of surgical practice. Two failed. The data from these trials determines what treatment options are available to people diagnosed today.

This analysis puts the results side by side, drawing from the published trial data in the New England Journal of Medicine, the Journal of Clinical Oncology, JAMA Oncology, and the Lancet.

The Complete Comparison

The hazard ratio measures relative death risk. Below 1.0 means the experimental treatment reduced the risk of death compared to the control arm. The lower the number, the larger the benefit.

First-Line Immunotherapy: CheckMate-743 and KEYNOTE-483

Two trials produced FDA-approved immunotherapy regimens for untreated pleural mesothelioma.

CheckMate-743: The First Immunotherapy Approval

CheckMate-743 enrolled 605 people with previously untreated pleural mesothelioma and randomized them to nivolumab plus ipilimumab or standard chemotherapy (pemetrexed plus cisplatin or carboplatin).

The five-year follow-up data, published in 2026, showed the survival curves continued to separate over time. Among people with non-epithelioid cell types (sarcomatoid and biphasic), the benefit was dramatic: 12% were alive at five years on immunotherapy versus 1% on chemotherapy.

KEYNOTE-483: Adding Immunotherapy to Chemotherapy

KEYNOTE-483 tested a different approach: adding pembrolizumab (Keytruda) to standard chemotherapy rather than replacing it.

The response rate of 52% is the highest recorded in any first-line mesothelioma trial. The FDA approved this combination in September 2024, giving people with mesothelioma two immunotherapy-based first-line options.

Second-Line Treatment: CONFIRM

For people whose mesothelioma has returned after initial treatment, the CONFIRM trial provided the first randomized evidence for second-line immunotherapy.

The trial enrolled 332 people with relapsed mesothelioma and demonstrated a 28% reduction in the risk of death (HR 0.72). This established nivolumab as a treatment option after chemotherapy fails.

The Trial That Changed Surgery: MARS 2

For decades, surgery was considered central to mesothelioma treatment. MARS 2 challenged that assumption.

The trial randomized 335 people to either chemotherapy followed by extended pleurectomy/decortication or chemotherapy alone. The results were definitive: people in the surgery arm had worse outcomes.

This does not mean surgery has no role. The trial tested one specific surgical approach (EPD) in a broad population. Pleurectomy/decortication at high-volume centers and HIPEC for peritoneal mesothelioma were not tested and continue to show strong outcomes in other data.

Emerging Approaches: ATOMIC-Meso and DREAM3R

ATOMIC-Meso: A Breakthrough for Non-Epithelioid Disease

ATOMIC-Meso tested pegargiminase (ADI-PEG20), an arginine-depleting enzyme, added to chemotherapy in people with non-epithelioid mesothelioma, the subtypes that respond least well to standard treatment.

The three-year survival rate quadrupled. For people with sarcomatoid or biphasic cell types, this represented the first treatment to show a meaningful survival benefit specifically in their subgroup.

DREAM3R: Promising Numbers, Inconclusive Results

DREAM3R tested durvalumab plus chemotherapy and produced the highest response rate (58%) of any Phase 3 mesothelioma trial. But the trial was stopped early after enrolling only 174 of a planned 480 participants, and the overall survival difference did not reach statistical significance (HR 0.92).

The response rates suggest durvalumab has activity against mesothelioma. But without enough patients to prove a survival benefit, the data remains inconclusive.

The Failures: DENIM

The DENIM trial tested a dendritic cell vaccine as maintenance therapy after chemotherapy. It did not improve overall survival. The failure reflects the challenge of translating immunological concepts into clinical benefit for mesothelioma.

Not every approach works. For the 92 trials currently recruiting, including CAR-T cell therapies and targeted therapies, these failures help define where future research should focus.

What the Data Means for Treatment Decisions

The trial results point to several clear patterns:

Immunotherapy has changed first-line treatment. Both CheckMate-743 and KEYNOTE-483 demonstrated survival benefits over chemotherapy alone. For the first time, people with mesothelioma have two FDA-approved immunotherapy options as initial treatment.

Cell type matters more than ever. People with epithelioid mesothelioma respond to both chemotherapy and immunotherapy. People with sarcomatoid or biphasic disease benefit most from immunotherapy (CheckMate-743) and arginine depletion (ATOMIC-Meso), but respond poorly to chemotherapy alone.

Surgery remains debated. MARS 2 showed that adding surgery to chemotherapy did not help in a general population. But specialized surgical approaches at high-volume centers continue to produce strong outcomes in selected patients, particularly for peritoneal mesothelioma treated with HIPEC.