Baylor-Duke Trial Tests Immunotherapy Plus Chemo Before Mesothelioma Surgery

A new clinical trial at Baylor College of Medicine and Duke University is enrolling people with operable pleural mesothelioma to test whether adding chemotherapy to dual immunotherapy before surgery improves outcomes.

The NEMO trial (NCT05932199) is a Phase Ib/IIa study comparing two approaches: immunotherapy alone versus immunotherapy combined with platinum-based chemotherapy, both given before surgical resection. It aims to enroll 52 people and is currently recruiting at both sites.

What the Trial Is Testing

The central question is straightforward: does adding chemotherapy to immunotherapy before surgery produce better results than immunotherapy alone?

All participants receive durvalumab (a PD-L1 inhibitor) and tremelimumab (a CTLA-4 inhibitor), two immune checkpoint inhibitors that work by different mechanisms to help the immune system recognize and attack cancer cells.

Participants are randomized to one of two arms:

• Arm A: Durvalumab plus tremelimumab (immunotherapy only)
• Arm B: Durvalumab plus tremelimumab plus cisplatin or carboplatin and pemetrexed (chemoimmunotherapy)

Both groups receive three cycles of their assigned treatment before surgery. After the operation, all participants receive durvalumab and tremelimumab for five additional cycles, followed by durvalumab alone for the remainder of a 12-month adjuvant period.

Who Can Participate

The trial is open to adults aged 18 and older with malignant pleural mesothelioma of any histologic subtype who are being considered for surgical resection. Key eligibility requirements include:

• No prior treatment for mesothelioma
• Potentially resectable disease (determined by the surgical team)
• Any PD-L1 status
• ECOG performance status adequate for surgery

People who have previously received PD-1 or PD-L1 inhibitor therapy are not eligible.

Why This Trial Matters

The NEMO trial builds on earlier work that showed dual immunotherapy before surgery could reshape the immune response to mesothelioma. A predecessor study at Baylor (NCT02592551), published in Clinical Cancer Research in 2023, enrolled 20 people and found that the combination of durvalumab and tremelimumab produced significantly longer survival than durvalumab alone.

In that earlier trial, median overall survival had not been reached at 34.1 months of follow-up for the combination arm, compared with 14 months for single-agent immunotherapy. About 35% of surgical participants showed meaningful tumor regression.

The NEMO trial takes the next logical step by asking whether chemotherapy, which has its own anti-tumor effects and may also enhance the immune response, can further improve on those results.

The Bigger Picture

This trial is part of a broader shift in mesothelioma treatment. For years, the standard approach was surgery followed by chemotherapy, or chemotherapy alone for people who were not surgical candidates. Immunotherapy entered the picture primarily for inoperable disease, after the CheckMate 743 trial established nivolumab plus ipilimumab as a treatment option.

Now, multiple research groups are testing whether moving immunotherapy earlier in the treatment sequence, before surgery, can produce better long-term outcomes. A Georgetown-Johns Hopkins trial published in Nature Medicine in 2025 showed that perioperative nivolumab plus ipilimumab produced a median survival of 28.6 months in people with operable disease.

Recent immunotherapy advances have extended three-year survival to approximately 23% for people with advanced mesothelioma. By combining immunotherapy with surgery, researchers hope to push survival rates higher for people whose disease can be surgically removed.

Limitations to Consider

The NEMO trial is an early-phase study designed primarily to assess safety and feasibility. With a target of 52 participants across two arms, it is not large enough to definitively establish whether one approach is superior to the other.

The trial is available only at two academic medical centers. People living far from Houston or Durham may face logistical challenges in participating, though both sites have experience coordinating care for out-of-state participants.

Results will take time. Enrollment, treatment, surgery, and follow-up could span several years before meaningful survival data are available.