Study to Test Nivolumab and Chemotherapy for Mesothelioma

Researchers in Germany are recruiting patients for a trial of nivolumab and chemotherapy for pleural mesothelioma patients who have had surgery.

Nivolumab (Opdivo) is an immunotherapy drug similar to pembrolizumab (Keytruda). It blocks a protein that helps mesothelioma cells hide from the immune system. Nivolumab is most often used for patients with non-small cell lung cancer.

The multicenter German study will test if a combination of nivolumab and chemotherapy can help keep tumors from growing back after mesothelioma surgery. Previous studies suggest that it has the potential to do so.

How Immune Checkpoint Inhibitors Work

Immune checkpoint inhibitors like nivolumab, pembrolizumab, and ipilimumab (Yervoy) are a major focus for mesothelioma researchers. Mesothelioma cells are notoriously tenacious. They often fail to respond to standard cancer treatments. This includes Alimta, the main chemotherapy drug for mesothelioma. 

But nivolumab and chemotherapy might be the answer. Nivolumab blocks the tumor-promoting protein PD-L1. Research suggests that 3 out of 4 mesothelioma patients have elevated PD-L1 levels. PD-L1 helps mesothelioma tumors grow by making it harder for the immune system to detect them. 

Japanese researchers published a nivolumab trial called MERIT earlier this year. It showed nivolumab was “clinically effective, safe, and cost-effective” as a second- or third-line treatment for relapsed mesothelioma.

Nivolumab and Chemotherapy Provide a ‘One-Two’ Punch

 The German trial goes by the acronym NICITA (nivolumab and chemotherapy in pleural mesothelioma after surgery). The trial will include 92 pleural mesothelioma patients who had surgery. They may or may not have also had HITHOC. This treatment involves rinsing the chest cavity with heated chemotherapy drugs.

All patients will receive up to four rounds of chemotherapy with Alimta. Half of the patients will also get nivolumab. These patients can continue on nivolumab for up to twelve cycles. Researchers hope that the nivolumab will make the cells more vulnerable to chemotherapy. 

The real test for nivolumab and chemotherapy will be how long it takes for patients to need another mesothelioma treatment. 

“The secondary endpoints include progression-free survival, overall survival, proportion of patients with treatment beyond progression, duration of treatment beyond progression in this population, and quality of life,” writes study author Rajiv Shah. Dr. Shah is with the German Center for Lung Research at Heidelberg University.

Bristol-Myers Squibb, which makes nivolumab, is a sponsor of the study. 

Earlier this year, the US FDA approved a combination of Opdivo and Yervoy for pleural mesothelioma. It was the first drug treatment approved for mesothelioma since Alimta in 2004. 

Source:

Shah, R, et al, “A Phase II Trial of Nivolumab With Chemotherapy Followed by Maintenance Nivolumab in Patients With Pleural Mesothelioma After Surgery: The NICITA Study Protocol”, October 14, 2020, Clinical Lung Cancer, https://www.clinical-lung-cancer.com/article/S1525-7304(20)30307-7/fulltext

AOE, K, “A phase II study of nivolumab: a multicenter, open-label, single arm study in malignant pleural mesothelioma (MERIT)”, Epub, January 7, 2020, Annals of Oncology, https://www.researchgate.net/publication/328379057