Race to FDA Approval: Which Therapy Is Next for Mesothelioma?

After 15 years of not approving any new therapies for mesothelioma, the U.S. Food and Drug Administration approved two in consecutive years.

The FDA green-lit a tumor treating fields device in 2019 and an immunotherapy regimen in 2020.

So the question now is, “What’s next?”

The FDA first approved the NovoTTF-100L System, which is now called Optune Lua. The tumor treating fields device was the first approval since the FDA pushed forward the chemotherapy drugs cisplatin and pemetrexed.

The FDA most recently approved Opdivo and Yervoy, two immunotherapy drugs to be used together for malignant mesothelioma.

Three therapies seem at the doorstep of FDA approval for mesothelioma. They have a chance to be approved for similar scenarios as the last two: unresectable malignant mesothelioma (ineligible for surgery).

 

ONCOS-102

ONCOS-102 is an oncolytic adenovirus that stimulates the immune response to mesothelioma. In other words, it’s a virotherapy that transitions into an immunotherapy for mesothelioma.

ONCOS-102 delivers a virus into the tumor microenvironment. The virus breaks apart mesothelioma cells, which release hidden antigens. The virus then relays these antigens to the immune system, which swarms to the tumor environment.

The FDA fortunately already favors ONCOS-102. The agency gave “fast-track designation” to the therapy last month. ONCOS-102 fares better than chemotherapy regarding survival, and it has fewer side effects.

The FDA recognizes the lack of therapeutic options for mesothelioma, especially for cases too severe for surgery. The fast-track designation allows faster review and approval.

 

Keytruda

The FDA already gave limited and specific approval for Keytruda, the immunotherapy brand name drug for pembrolizumab. The drug can only be used for cases with high expression of PD-1/PD-L1, which is a protein connection that suppresses the immune system.

With the approval of Opdivo, another PD-1/PD-L1 checkpoint inhibitor, there seems to be two options now for these specific cases. The next step is Keytruda gaining more expansive approval, possibly for any unresectable malignant mesothelioma cases.

The PROMISE study had discouraging survival results. Keytruda did not outperform chemotherapy, which turned some experts away from the drug. Others refuse to give up hope.

The best bet seems to be pairing Keytruda with chemotherapy, surgery or radiation. For instance, a trial at Abramson Cancer Center at the University of Pennsylvania is using the immunotherapy drug with image-guided surgery.

 

Durvalumab

A phase 3 trial testing durvalumab is now recruiting for two locations in the United States: Michigan Medicine in Ann Arbor and Metro Minnesota Community Oncology Research Consortium in Saint Louis Park.

Durvalumab, the generic drug name for the brand Imfinzi, is a PD-L1 checkpoint inhibitor. It works similar to Keytruda and Opdivo — stopping the PD-L1 protein from sidestepping the immune system’s T-cell guardians.

Researchers use durvalumab with chemotherapy. The results indicate the pair works better than chemotherapy alone:

• Durvalumab plus chemotherapy led to a median survival of 20.4 months and a 44% two-year survival rate.
• Chemotherapy alone has a median survival of 12 months and a two-year survival rate closer to 25%.