Phase 3 Clinical Trial to Test Durvalumab for Mesothelioma

A potential new first-line immunotherapy treatment for mesothelioma is now recruiting patients for a phase 3 clinical trial.

The trial will compare the immunotherapy drug durvalumab (IMFINZI) combined with chemotherapy against chemotherapy alone. 

Results from the phase 2 trials of this combination released last year were promising. Tests showed that it extended mesothelioma survival by about 8 months with no debilitating side effects. 

The randomized phase 3 clinical trial will try to confirm these results in a larger group of people.

Mesothelioma Treatment with Durvalumab

Durvalumab is an immune checkpoint inhibitor. Immune checkpoint inhibitors deactivate a cancer cell survival mechanism that helps cancer cells evade the immune system. Pleural mesothelioma and other types of cancer use proteins like PD-1 to protect themselves. 

Durvalumab and other immune checkpoint inhibitors (such as Keytruda) block PD-1. With their defenses down, cancer cells are more vulnerable to treatments like chemotherapy. 

The phase 3 clinical trial is especially relevant for people with unresectable mesothelioma. Right now, chemotherapy is the best hope for these patients. But chemotherapy is only marginally effective. If durvalumab helps it work better, even patients with inoperable mesothelioma might live longer. 

From Phase 2 to Phase 3 Clinical Trial

The earlier trials involved mesothelioma researchers in Australia, the US, and New Zealand. In the US, the study included 55 mesothelioma patients from 15 cancer centers. Researchers at Johns Hopkins led the research.

In the original study, mesothelioma patients got six treatments with Alimta, cisplatin and durvalumab. The treatments happened every three weeks. After three weeks, patients received just durvalumab for up to a year. It was the first study to show survival times longer than 20 months for patients with inoperable mesothelioma.

The phase 3 clinical trial is called DREAM3R. It will also take place in Australia, New Zealand, and the US. It will follow a similar protocol.

“We expect that the DREAM3R trial will be a particularly good treatment option for the 75% of MPM patients with epithelioid subtype, which is associated with significantly better outcomes from chemotherapy than the non-epithelioid subtype,” says lead US investigator Patrick Forde, MD, of Johns Hopkins University.

The phase 3 clinical trial aims to enroll 480 mesothelioma patients between 18 and 70. Patients must not have had any treatment yet and their cancer must not be removable surgically. 

Malignant mesothelioma affects more than 2,500 people in the US every year. Most of those people have the pleural type of mesothelioma which affects the lungs. If the new trial shows a clear benefit, durvalumab and chemotherapy could become a new first-line treatment for pleural mesothelioma. 

Sources: 

“Durvalumab immunotherapy proceeds to phase 3 trial for malignant pleural mesothelioma”, March 17, 2021, News Release PrECOG Research Group website, https://www.precogllc.org/news/durvalumab-immunotherapy-proceeds-to-phase-3-trial-for-malignant-pleural-mesothelioma

“Research Story Tip: Chemotherapy/Immunotherapy Combo Shows Promise for First-Line Treatment of Mesothelioma”, Johns Hopskins new release, June 11, 2020, https://www.hopkinsmedicine.org/news/newsroom/news-releases/research-story-tip-chemotherapyimmunotherapy-combo-shows-promise-for-first-line-treatment-of-mesothelioma