Immunotherapy Trial for Mesothelioma Shows Early Promise

The immunotherapy drug avelumab showed promising results in a recent phase I clinical trial for malignant mesothelioma, raising hopes as a future second-line therapy.

The clinical trial included 53 patients with pleural or peritoneal mesothelioma. It was part of the JAVELIN development program for avelumab, a series of clinical studies testing the drug on about 2,200 patients with more than 15 types of cancer. Merck KGaA, Darmstadt, Germany and Pfizer are co-developing and marketing avelumab.

Medical oncologist and mesothelioma specialist Dr. Raffit Hassan of the National Cancer Institute (NCI) presented the clinical trial results earlier this month at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

He expressed considerable optimism about the outcome.

The drug reduced tumor size in nearly 10 percent of patients. Median progression-free survival — the length of time a patient lives with the disease before it begins to worsen — was 17.1 weeks. The majority of trial participants tolerated the drug well.

“These data add to the growing body of evidence for avelumab, indicating efficacy and a favorable safety profile in multiple cancers, which supports ongoing development,” said Chris Boshoff, vice president and head of early development, translational and immuno oncology at Pfizer Oncology. “We are making meaningful advances for a broad range of patients with cancer.”

A Need for Second-Line Mesothelioma Treatments

All patients involved in the study were diagnosed with unresectable mesothelioma and experienced disease progression after standard chemotherapy.

There are currently no FDA-approved second-line treatments for mesothelioma available to this patient group, although several are in the developmental stage. Avelumab is one of them.

Avelumab works by attacking PD-L1, a protein found on the surface of most cancer cells that prevents a person’s immune system from rejecting the cancer. Avelumab essentially unmasks the cancer cells and allows the immune system to kill them.

“This database is the largest study to date of patients with mesothelioma treated with an anti-PD-L1 antibody,” Hassan said during the presentation. “Ongoing follow up will further characterize durability of the clinical benefit.”

PD-L1 has become a popular target for several immunotherapy drugs tested on various cancers. Many in the medical community believe immunotherapy is the key to future advancements in treatment.

Avelumab is expected to move to phase II testing for mesothelioma by 2017, which will further explore the safety and effectiveness of the drug on a larger patient group. The drug showed considerable effectiveness for non-small cell lung cancer in a phase Ib trial. Researchers are now testing the drug with other diseases, including cancers of the head and neck, kidneys, ovaries, stomach and bladder.

Other Mesothelioma Trials at NCI

Although the avelumab study for mesothelioma is currently closed, Hassan is lead investigator for several other mesothelioma clinical trials at the National Cancer Institute that are currently recruiting patients.

Anetumab ravtansine, also known as BAY 94-9343, is another immunotherapy drug being explored in a phase II trial for mesothelioma. This drug targets mesothelin, a protein that researchers have connected to tumor progression and resistance to chemotherapy.

Several types of cancer cells produce too much mesothelin, including mesothelioma, pancreatic cancer and ovarian cancer. The protein is a common target for immunotherapy drugs used to treat these cancers.

As part of a randomized trial, researchers will measure anetumab ravtansine against the chemotherapy drug vinorelbine.

Hassan presented trial data for BAY 94-9343 at the ASCO annual meeting earlier this month. In an earlier phase I study of mesothelioma patients who received the drug as a second-line therapy, BAY 94-9343 shrank tumors in 50 percent of patients and had tolerable side effects.

The search for a reliable second-line treatment is critical for patients because the benefits of standard chemotherapy often do not last long in the fight against mesothelioma.