Gene Therapy Trial for Mesothelioma Opens Internationally

A long-awaited phase III clinical trial of a novel gene therapy could change malignant pleural mesothelioma treatment in the future.

The trial, which will include almost 50 locations around the world, opens this month for mesothelioma patients whose standard treatment has stopped working.

The gene therapy drug, called TR002, is also a form of immunotherapy. It will be used in combination with gemcitabine chemotherapy in a second-line setting.

“We can’t predict what the outcome will be, but we’re very excited about the potential of this treatment, and the fact there may be another drug in the armamentarium for these patients,” principal investigator Dr. Daniel Sterman, New York University Langone Medical Center, told the Mesothelioma Center at Asbestos.com.

TR002 Study Culminates Decades of Research

The randomized trial is the culmination of more than 20 years of research that began at the University of Pennsylvania’s Perelman School of Medicine under Dr. Steven M. Albelda. It could be the final step before FDA approval.

TR002 is a genetically-engineered adenovirus that triggers the anti-tumor effects of interferon, a naturally-occurring protein that kills cancer cells.

In the trial, TR002 will be given just once by catheter directly into the pleural cavity. It works like a tumor vaccine inside the lining around the patient’s lung.

Chemotherapy with gemcitabine will follow 14 days later and continue until disease progression occurs.

“We deliver a virus which has been modified so it can’t reproduce itself in humans, but retains its ability to deliver genetic material to human cells,” Sterman explained. “The virus delivers its cargo, then is recognized by the immune system and is destroyed.”

When Sterman started working with gene therapy in the early 1990s, he was just beginning his medical career as a resident assisting Albelda at the University of Pennsylvania. The two have played a prominent role in the field’s development ever since.

“We hope this novel intervention will change the way some patients with mesothelioma are treated,” Sterman said. “We also hope to improve their quality of life, and we think that’s incredibly exciting.”

Earlier Studies Have Been Impressive

Their optimism is based on years of previous studies conducted as the drug and its novel delivery mechanism worked through the FDA approval process.

A phase II study of TR002, completed in 2016 at the University of Pennsylvania, reported an 87.5 percent disease control rate for patients who were either failed by standard chemotherapy or newly diagnosed.

As a second-line treatment, the 40 patients in the phase II study had a median survival of 17 months, almost double the historical control for survival. The two and three-year survival rates were 25 and 20 percent, respectively.

The new phase III study is looking for about 300 patients whose chemotherapy or immunotherapy combination has failed.

Cancer centers in Russia, Canada, Australia, the United Kingdom and the United States are expected to participate.

“Hypothetically, we have a chance — we hope to prove — that we can double survival in this second-line setting,” Sterman said. “There are other things we also hope to do along the way, like getting this drug into earlier-stage patients in combination with standard-of-care treatment, or with immunotherapy, or a combination.”

The University of Toledo Eleanor Dana Cancer Center in Ohio was the first to enroll a patient in the phase III trial last month. The New York University School of Medicine, the University of Pennsylvania and several others around the country will follow soon.

Trizell, a gene therapy specialty company in Europe, is sponsoring the trial.

“This is what the mesothelioma field needs, more phase III clinical trials. Right now, there are very few of them, some of which are turning out negative,” Sterman said. “We need definitive answers to what the best treatments are, so we can improve the quality and quantity of life for these patients with this horrible cancer.”

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