Study: Cancer Enzyme Slows Growth of Pleural Mesothelioma

Patients with pleural mesothelioma may extend their survival by an estimated 30% when the latest anti-cancer enzyme is added to standard chemotherapy, according to a recently completed study.

AGI-PEG 20 showed unprecedented effectiveness when treating patients with sarcomatoid mesothelioma and biphasic mesothelioma – the most treatment-resistant subtypes – in an international, multicenter, phase II/III clinical trial known as ATOMIC Meso.

The enzyme works by limiting an amino acid known as arginine that often fuels tumor cells. It depletes its effectiveness in promoting tumor growth, leading to longer survival. 

“The results were astonishing to me,” Dr. Peter Szlosarek, principal investigator and medical oncologist at UK Barts Cancer Institute in London, England, told The Mesothelioma Center at Asbestos.com. “The response was robust from the beginning.”

Anti-Cancer Enzyme Makes Chemotherapy More Effective

The study compared patients being treated with traditional pemetrexed and cisplatin chemotherapy to those using ADI-PEG 20 and the chemotherapy combination.

All patients were previously untreated, unresectable and diagnosed with either sarcomatoid or biphasic mesothelioma. Those patients, typically with a median survival of less than six months, were randomized in a double-blind clinical trial. 

Epithelioid mesothelioma is the most treatable and common subtype of mesothelioma that affects close to 70% of the patients being diagnosed. They were not included in the study.

The trial involved several of the leading cancer centers in the U.S. for treatment, including Moffitt Cancer Center in Tampa, Greenebaum Cancer Center in Baltimore, University of Chicago Cancer Center, Mayo Clinic in Rochester, Minnesota, and M.D. Anderson Cancer Center in Houston.

Those being treated with ADI-PEG 20 in combination with chemotherapy had a median survival of 9.3 months compared to 7.6 months for those receiving just the chemotherapy. 

Progression-free survival was 6.1 months for the ADI-PEG 20 patients, compared to 5.5 months for the placebo control arm.

A few of the patients in the study lived more than three years, an unheard-of result for the subtypes being treated.

There were few dose-limiting toxicities in the mesothelioma clinical trial. Most of the adverse side effects seen were considered mild to moderate and many were related to the chemotherapy and not the ADI-PEG 20.

“The Atomic Meso, without a doubt, offers patients with nonepithelioid mesothelioma a safe and novel triplet chemo regimen,” said Szlosarek, who has been studying the combination with several other tough-to-treat cancers. “This [study] heralds exciting times ahead for patients suffering various cancers.”

Manufacturers Will Seek FDA Approval

ADI-PEG 20 is a product of Polaris Group, a multinational biotechnology company focused on the development of the latest anti-cancer therapies.

Its plan is to proceed with regulatory submissions in the United States and seek U.S. Food and Drug Administration approval for mesothelioma treatment in 2023.

The FDA approved the use of an immunotherapy combination involving Opdivo and Yervoy in 2020, the first approval for first-line pleural mesothelioma treatment in 16 years.

With Szlosarek’s leadership, Polaris is working toward another study that will combine the immunotherapy treatment with ADI-PEG 20. Szlosarek has worked with ADI-PEG 20 for almost two decades as a cancer tool.

“We are pleased to report the phase II/III data showing that ADI-PEG 20 can significantly extend overall survival in patients with MPM [malignant pleural mesothelioma]. ADI-PEG 20 is the first arginine-degrading therapeutic to show positive topline results in a pivotal trial as a combination therapy for the treatment of MPM,” said Howard Chen, chairman of Polaris. “The results pave the way towards our working with the regulators to bring this novel biologic to patients with MPM.”

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