By: Patricia Inacio, PhD
An upcoming Phase 2 trial will explore the safety and effectiveness of a combo therapy — Opdivo (nivolumab) and MTG201 – for the treatment of malignant pleural mesothelioma. The trial will soon be looking for participants who received prior chemotherapy.
Mesothelioma is a rare type of cancer, commonly linked to exposure to asbestos, that often forms on the thin protective tissues that cover the lungs — pleural mesothelioma — or the abdomen, called peritoneal mesothelioma.
Patients are often treated with a combination of chemotherapy, radiotherapy, and surgery. But this usually leads to only minor improvements in survival outcomes.
“Progress in advancing long-term survival in pleural mesothelioma has been minimal for decades,” Bryan Burt, associate professor of surgery at Baylor College of Medicine and a member of the Dan L Duncan Comprehensive Cancer Center, said in a press release. “The benefit of the current standard treatments for pleural mesothelioma has plateaued.”
Now, researchers at the Mesothelioma Treatment Center at the Baylor College of Medicine Lung Institute are looking at more efficient ways of treating the disease. They are combining an approved immunotherapy with a new treatment that accelerates cell death.
Specifically, the open-label Phase 2 trial (NCT04013334) — to be conducted at the Baylor College of Medicine — will assess a combination of Opdivo and MTG201 in 12 people with malignant pleural mesothelioma who failed to respond to previous treatment with chemotherapy.
Opdivo, by Bristol-Myers Squibb, is a kind of immunotherapy called an immune checkpoint inhibitor. It targets the PD-1 protein on the surface of immune cells, and prevents its interaction with cancer cells. This prevents tumors to evade an immune attack.
However, in cancers like mesothelioma, where few immune cells exist, it’s not enough to activate the immune system. Instead, immune cells need to be attracted into the tumor.
MTG201, developed by MTG Biotherapeutics, is an inactivated adenovirus that selectively targets cancer cells and induces cell death. As the cancer cells die, they release tumor antigens — proteins that induce an immune response — that lure immune cells into the tumor environment.
Together with Opdivo, this is thought to increase the immune system’s response against the tumor.
In the Phase 2 trial, participants will receive four doses of MTG201 injected directly into the tumor. Opdivo will be given into the blood at a dose of 480 mg, every four weeks until disease progresses.
The trial’s primary goal is to determine the percentage of participants who respond to the treatment. Secondary goals include determining the duration of the response, and the length of time patients live without cancer progression.
The combo therapy has shown promising results in animal models of mesothelioma, where cell death caused by MTG201 boosted responses to Opdivo. The treatment also has stimulated the immune system to attack the tumor.
“This therapy eradicates mouse mesothelioma tumours, rapidly and consistently in an aggressive mouse model of mesothelioma,” said Burt, the principal investigator of this study.
The results of the Phase 2 trial will show whether the new combo therapy is a more efficient way of treating people with malignant pleural mesothelioma, especially those who failed to respond to standard therapy.
“Ultimately, individual patients will respond to different approaches,” said Robert Taylor Ripley, director of the Mesothelioma Treatment Center and associate professor of surgery at Baylor.
“I suspect that an array of therapeutic options will be necessary to provide effective therapies for all patients. Clinical trials will help define which patient will respond and which therapies should routinely be utilized while avoiding ineffective treatment,” Ripley added.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.