GPS Vaccine Plus Opdivo Shows Promise for Pleural Mesothelioma

Research and clinical trials

A new targeted cancer vaccine combined with the immunotherapy drug Opdivo has shown surprising efficacy in mesothelioma patients whose disease no longer responds to standard chemotherapy.

In a phase I clinical trial at Memorial Sloan Kettering Cancer Center, the galinpepimut-S vaccine, also known as GPS, produced an impressive antitumor synergy with Opdivo, based on early data.

GPS targets the WT1 protein, which is expressed at high levels in various cancers but is rarely seen in normal adult cells. The protein was particularly resistant to standard chemotherapy.

The vaccine works by stimulating a strong T-cell immune response against WT1 antigen. Aside from a temporary low-grade reaction at the injection site, the vaccine showed few side effects.

The vaccine was developed by SELLAS Life Sciences Group, a New York City-based biopharmaceutical company. It has already received orphan drugs and fast-track designations from the US Food and Drug Administration.

“Patients treated in this group appear to live longer than expected,” said Dr. Angelos Stergiou, president and CEO of SELLAS, of the Mesothelioma Center at Asbestos.com. “It was absolutely wonderful.”

Vaccine combination can extend survival

Only the first four patients in the study, all of whom were male, were included in the early data. Three have an epithelial cell type and one has a more difficult-to-treat sarcomatoid type. Two of the four were diagnosed with stage 4. All showed disease progression or were resistant to frontline chemotherapy.

All four received treatment for at least one month that included the GPS vaccine and Opdivo, also known as nivolumab. This drug is part of a first-line treatment recently approved by the U.S. Food and Drug Administration for the treatment of pleural mesothelioma.

The median progression-free survival was 8.8 weeks. The median overall survival was 35.4 weeks, which is the time when the data were taken. Stergiou expects the overall average survival to be significantly longer when the next report is submitted at the end of 2021.

In comparison, patients with relapsed or treatment-resistant mesothelioma had a median overall survival of 20 to 24 weeks.

“GPS provides ongoing support and memory for the immune system,” Sturgeo said. “Together, there is the potential to target and eliminate residual cancer.”

Most impressive was the patient with sarcomatoid mesothelioma, which is usually the most difficult to treat and comes with an estimated survival of 5 to 6 months from the time of diagnosis. The patient in this study was still alive after 25 months.

In a previous double-blind, placebo-controlled clinical trial, the GPS vaccine produced a median survival of 21.4 months for mesothelioma patients who had already completed multimodal therapy. The placebo group median survival was only 16.6 months.

The vaccine is also in different stages of development for use with multiple myeloma, ovarian cancer and a rare form of brain cancer.

GPS vaccine is effective in preventing recurrence

Previous research has shown that the effectiveness of the GPS vaccine is best when used to prevent disease recurrence, or in combination with standard treatment.

As a second-line treatment, it has been praised as a potentially effective method of preventing or delaying recurrence in patients who have achieved complete remission or have minimal residual disease.

“Even with someone with disease progression, there can be benefits from a survival perspective,” Sturgeo said. “That’s really where we are now.”

The FDA fast-track is designed to expedite drug review and aid development, especially for rare diseases such as mesothelioma, an aggressive cancer for which there is no definitive cure.

Mesothelioma results from inhalation or ingestion of microscopic asbestos fibers and is diagnosed in an estimated 3,000 people annually in the United States

The clinical trial at Memorial Sloan Kettering will continue to accept new patients, and the vaccine with different formulations is expected to be examined in other studies.

“People shouldn’t think this is some kind of miracle drug, but we see early on that there is real promise for mesothelioma,” Stergo said. “This could be a safe and secure treatment for patients to help prolong survival. We are excited to continue the development process.”