Mesothelioma Clinical Trial Involves Immunotherapy Before Surgery

Three of the country’s leading cancer centers have opened a collaborative clinical trial that potentially could change surgical treatment of mesothelioma.

Researchers will measure the safety and efficacy of using two different immunotherapy drug regimens — Opdivo (nivolumab) and Yervoy (ipilimumab) — beginning 42 days before surgery.

The hope is that at least one will make surgical resection more effective.

Sidney Kimmel Cancer Center at Johns Hopkins University, MD Anderson Cancer Center at the University of Texas and Greenebaum Cancer Center at the University of Maryland are working together to enroll at least 30 patients for the study.

Principal investigator Dr. Patrick Forde, a thoracic oncologist at Johns Hopkins, spoke about the study to several patients and patient advocates in a conference call orchestrated by the Mesothelioma Applied Research Foundation in Washington, D.C.

“The study is building on work already done for other cancers,” Forde said. “Initial results in other cancers, such as breast and lung cancer, have been promising with this approach.”

Yervoy Delivered Just Once in Clinical Trial

The study wants 15 patients receiving Opdivo before surgery and another 15 taking Opdivo and Yervoy.

Opdivo will be given 42, 28 and 14 days before surgery. Yervoy will be administered just once, on day 42.

The study also allows for patients to continue receiving regular immunotherapy treatments after surgery for up to one year or until disease progression.

“We know from other cancers that giving immunotherapy prior to surgery has been shown to lead to regression of the tumor and infiltration of the immune system attacking the cancer,” Forde said. “We know from other cancers that it can be effective.”

Both drugs are known as immune checkpoint inhibitors.

The two drugs target different surface proteins, but they work in similar ways, negating their effectiveness that restricts a patient’s immune system from stopping the tumors.

Two Surgeries Eligible for Immunotherapy Trial

The eligibility of the clinical trial will include patients undergoing either a pleurectomy and decortication or an extrapleural pneumonectomy surgery.

It also will include patients with either the epithelioid or biphasic cell type of mesothelioma, but not those with sarcomatoid.

Although neither Opdivo and Yervoy have been approved by the U.S. Food and Drug Administration for use with mesothelioma, the drugs already have shown effectiveness without surgery for a small percentage of patients.

Both drugs are manufactured by pharmaceutical giant Bristol-Myers Squibb, which is helping fund this latest study.

In two separate studies published in 2019, researchers from France and the Netherlands showed the combination of Opdivo and Yervoy created a synergy that helped stop or slow pleural mesothelioma tumors in a second-line setting.

Earlier Opdivo/Yervoy Studies Show Promise

The study in France involved 125 inoperable patients, all of whom entered after chemotherapy failed.

Results included a 44% disease control rate for patients taking Opdivo and 50% for those with the Opdivo and Yervoy combination.

The median overall survival was nearly one year for Opdivo and 15.9 months for the combination.

Forde also was involved in another study using Opdivo before aggressive surgery for patients with lung cancer.

He published results in 2017 that included a 90% tumor regression in nine of the 21 patients.

Bristol-Myers Squibb is sponsoring another mesothelioma clinical trial that began in 2017 at cancer centers across the U.S.

The trial is measuring the effectiveness of Opdivo and Yervoy compared with standard chemotherapy for inoperable patients.

In this latest trial, patients and their medical providers will have the option of doing standard chemotherapy before and/or after surgery, along with the immunotherapy drugs.

They also may have the option of radiation therapy after the surgery.

Surgical resection after immunotherapy will allow for a more in-depth assessment of immune and pathologic response rates.

“In general, these drugs are well tolerated,” Forde said. “We’ve also learned that a lot of times, these different forms of treatment can synergize in a positive way.”