Drug manufacturers announced disappointing ends recently to two different clinical trials involving pleural mesothelioma, dampening earlier enthusiasm over the promise of immunotherapy.
Anetumab ravtansine, manufactured by Bayer, and tremelimumab, from drugmaker AstraZeneca, failed an effectiveness test as a stand-alone, second-line treatment for mesothelioma, according to both manufacturers.
“Malignant pleural mesothelioma is a very difficult-to-treat tumor, and we had hoped for a better outcome for patients,” said Robert LaCaze, an executive vice president at Bayer.
Although trial officials have not released their results, LaCaze confirmed the primary endpoint of progression-free survival was not met.
Researchers are studying anetumab ravtansine (BAY 949343) with six different types of cancer, while still showing effectiveness in combination with other drugs for treating mesothelioma.
Tremelimumab is an immunotherapy agent created with human antibodies and has the ability to unmask the cancer cells, allowing a patient’s own immune system to attack.
While it has shown effectiveness with non-small cell lung cancer, it did not improve survival in a large, multicenter mesothelioma trial.
Although the trial was suddenly stopped in 2016, The Lancet Oncology in July published results of the phase II trial, which involved 105 centers across 19 countries. It included 20 cancer centers within the U.S.
The trial originally launched in 2013, and 571 patients were randomly selected to receive tremelimumab or a placebo.
Eighty percent of all patients in the trial died by 2016. The median overall survival was seven months for both groups. More than half of participants receiving tremelimumab experienced adverse side effects, while less than half in the placebo group suffered side effects.
“We are disappointed that tremelimumab did not demonstrate a survival benefit in this patient population,” Robert Iannone, a senior vice president of AstraZeneca said earlier. “We remain confident in its clinical activity in combination.”
The latest failure won’t be the end of tremelimumab, but it has changed the focus of its use in clinical trials.
A much smaller study in Italy, done previously with intensified scheduling of the drug, showed a 50 percent disease control rate and a 48.3 percent one-year survival rate.
The Lung Institute at the Baylor College of Medicine, under the direction of Dr. David Sugarbaker, is in the midst of a clinical trial involving tremelimumab in combination with durvalumab, another immunotherapy agent, in conjunction with surgery.
The recent failure of anetumab ravtansine also will alter its usage in clinical trials, but it remains a viable option as a combination drug for mesothelioma patients.
Anetumab ravtansine combines immunotherapy with cytotoxic therapy that targets the surface protein mesothelin, which is overexpressed in a majority of mesothelioma patients.
The National Cancer Institute and the University of Chicago Comprehensive Cancer Center are among a handful of centers studying anetumab ravtansine in combination with chemotherapy for mesothelioma.
The National Cancer Institute will soon announce the start of another clinical trial for mesothelioma that involves anetumab ravtansine in combination with pembrolizumab (Keytruda).
Sugarbaker, the most heralded surgeon in the mesothelioma community, already has talked about combining anetumab ravtansine with aggressive surgery and chemotherapy.
Bayer also recently sponsored a clinical trial for ovarian cancer patients involving anetumab ravtansine in combination with other drugs.
“Based on the available data, we remain committed to further evaluating the utility and safety of anetumab ravtansine across multiple tumor types with significant unmet medical needs,” LaCaze said.