8 Mesothelioma Trials Compared: Results Side by Side

Eight clinical trials have shaped how mesothelioma is treated in 2026. Two led to FDA approvals. One overturned a long-standing surgical practice. One failed outright. 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 published trial data in Lancet, the Journal of Clinical Oncology, JAMA Oncology, Lancet Oncology, Lancet Respiratory Medicine, and Nature Medicine.

The Complete Comparison

Eight trials, eight different questions, eight different answers. The table puts every endpoint that matters in one frame: regimen, phase, response rate, median overall survival, hazard ratio, and outcome.

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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. Above 1.0 (as in MARS 2) means the experimental arm did worse than the control.

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

Two trials produced FDA-approved immunotherapy regimens for untreated pleural mesothelioma. Both showed survival benefits over chemotherapy alone, but the two regimens reach the benefit through different mechanisms.

CheckMate-743: The First Immunotherapy Approval

CheckMate-743 (NCT02899299) enrolled 605 people with previously untreated pleural mesothelioma and randomized them to nivolumab plus ipilimumab or standard chemotherapy (pemetrexed plus cisplatin or carboplatin). The primary results were published in Lancet in 2021 (Baas et al.).

The five-year follow-up, published by Scherpereel and colleagues in the Journal of Clinical Oncology in 2026, showed the survival curves continued to separate over time (HR 0.74, 95% CI 0.62-0.88). Among people with non-epithelioid cell types, 12% were alive at five years on immunotherapy versus 1% on chemotherapy (HR 0.48).

In the initial Baas 2021 publication, the non-epithelioid subgroup had a median OS of 18.0 months on nivolumab plus ipilimumab versus 13.3 months on chemotherapy (HR 0.46). The two reports together establish nivolumab plus ipilimumab as the regimen with the largest absolute benefit for sarcomatoid and biphasic disease.

KEYNOTE-483: Adding Immunotherapy to Chemotherapy

KEYNOTE-483 (also known as CCTG IND.227; NCT02784171) tested a different approach: adding pembrolizumab (Keytruda) to standard chemotherapy rather than replacing it. The trial enrolled 440 people and was published in Lancet in 2023.

The 52% objective response rate is the highest reported in a first-line mesothelioma trial. The FDA approved this combination on September 17, 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 randomized evidence for second-line immunotherapy. Fennell and colleagues published the primary results (NCT03063450) in Lancet Oncology in 2021.

The trial enrolled 332 people with relapsed pleural or peritoneal mesothelioma after platinum-based chemotherapy (2:1 randomization, 221 nivolumab vs 111 placebo). The adjusted hazard ratio of 0.69 represents a 31% reduction in the risk of death. This established nivolumab as a treatment option after chemotherapy fails.

The Trial That Changed Surgery: MARS 2

For years, extended pleurectomy decortication was considered a cornerstone of mesothelioma treatment at specialist centers. MARS 2 (NCT02040272), led by Eric Lim and published in Lancet Respiratory Medicine in 2024, challenged that practice.

The trial randomized 335 people (169 to surgery plus chemotherapy, 166 to chemotherapy alone). The results: people in the surgery arm had worse outcomes.

This does not mean surgery has no role in mesothelioma care. The trial tested one specific surgical approach (extended pleurectomy decortication) in a broad population. HIPEC for peritoneal mesothelioma and other surgical strategies were not evaluated.

Emerging Approaches: ATOMIC-Meso and DREAM3R

ATOMIC-Meso: A Positive Trial for Non-Epithelioid Disease

ATOMIC-Meso (NCT02709512) tested pegargiminase (ADI-PEG20), an arginine-depleting enzyme, added to pemetrexed plus platinum chemotherapy in 249 people with non-epithelioid pleural mesothelioma. Szlosarek and colleagues published the results in JAMA Oncology in 2024.

For people with sarcomatoid or biphasic cell types, this was the first trial to show a survival benefit from a therapy designed specifically for non-epithelioid histology. Pegargiminase is not FDA-approved for mesothelioma as of May 2026.

DREAM3R: Still Enrolling

DREAM3R / PrE0506 (NCT04334759) is a Phase 3 trial testing durvalumab plus pemetrexed and platinum against chemotherapy alone in untreated advanced pleural mesothelioma. The planned enrollment is 480 patients.

As of May 2026, the trial is listed as active and enrolling on ClinicalTrials.gov. No efficacy results have been published. The only peer-reviewed publication to date is the design/protocol paper (Falk et al., BMJ Open 2022).

DENIM: A Negative Trial

The DENIM trial tested MesoPher, an autologous dendritic cell vaccine, as maintenance therapy after chemotherapy. Aerts and colleagues published the results (NCT03610360) in Lancet Oncology in 2024: the trial did not improve overall survival and did not meet its primary endpoint.

Perioperative Immunotherapy: Johns Hopkins

The Johns Hopkins perioperative trial (NCT03918252) tested neoadjuvant nivolumab alone or nivolumab plus ipilimumab, followed by surgery and up to one year of postoperative nivolumab. Reuss, Anagnostou, and colleagues published results in Nature Medicine in 2025.

Median follow-up was 43.2 months. The trial enrolled 30 patients across both arms, so the data is hypothesis-generating rather than definitive. It was the first mesothelioma trial to pair perioperative immune checkpoint blockade with circulating tumor DNA (ctDNA) minimal residual disease monitoring.

What the Data Means for Treatment Decisions

The trial results point to several clear patterns. Immunotherapy has changed first-line treatment, cell type matters more than ever, and one long-standing surgical approach is now in question.

Both CheckMate-743 and KEYNOTE-483 demonstrated survival benefits over chemotherapy alone, and people with mesothelioma now have two FDA-approved immunotherapy options as initial treatment.

Cell type matters. People with epithelioid mesothelioma respond to both chemotherapy and immunotherapy, while people with sarcomatoid or biphasic disease benefit most from the nivolumab plus ipilimumab combination (CheckMate-743) and pegargiminase plus chemotherapy (ATOMIC-Meso).

Surgery is under re-evaluation. MARS 2 showed that adding extended pleurectomy decortication to chemotherapy did not help in a general population, though HIPEC for peritoneal mesothelioma was not tested by MARS 2 and remains a distinct clinical question.