A leading biopharmaceutical company has halted a once-promising mesothelioma clinical trial involving CRS-207 — a listeria-based cancer vaccine — citing efficacy and financial concerns.
The phase II trial was designed to test the effectiveness and safety of CRS-207 when used in combination with pembrolizumab (Keytruda), a drug already proven effective with non-small cell lung cancer.
The trial, which began earlier this year, was being conducted at eight prominent cancer centers across the United States. It was funded by Aduro Biotech Inc., based in Berkeley, California.
“This was not the news everyone had hoped for,” Steve Isaacs, president and CEO of Aduro Biotech, said during a conference call with investors last week. “Sometimes the news isn’t what you want. We were hoping to deliver better news from the CRS program.”
Hope for Second-Line Treatment
Aduro Biotech was testing the drug combination in a second-line setting for the treatment of mesothelioma, ovarian cancer and gastric cancer. All three trials have stopped accepting new patients, although some treatments are continuing for now.
“The outcome is disappointing for a lot of reasons, but most importantly, for the cancer patients in dire need of new therapeutic options,” Isaacs said. “We’ll be working with investigators now in a manner that is in the best interest of the patients.”
Pleural mesothelioma has been especially difficult to treat, and advances have been slow.
A handful of specialty centers have been relatively successful with a multidisciplinary approach that includes surgery, chemotherapy and radiation, but the majority of patients still survive less than two years after a diagnosis.
And less than a third of the patients even qualify for surgery.
There currently is no second-line treatment for mesothelioma approved by the U.S. Food and Drug Administration (FDA). The estimated completion date for the CRS trial was originally set for March 2019.
According to Clinicaltrials.gov, cancer centers involved in the trial included:
- UCSF Comprehensive Cancer Center (San Francisco)
- H. Lee Moffitt Cancer Center (Tampa)
- University of Chicago Medical Center
- NIH National Cancer Institute (Bethesda, Maryland)
- Mayo Clinic (Rochester, Minnesota)
- Perlmutter Cancer Center at NYU Langone (New York)
- Cleveland Clinic
- Abramson Cancer Center at UPenn (Philadelphia)
Investigators at three of the centers declined comment this week, citing confidentiality and individual participation in the trial.
“We have a mantra at Aduro, and that’s ‘Follow the data,’” Isaacs said. “Sometimes that means making tough program decisions.”
Two-Drug Synergy Never Materialized
The company did not release any early results of the phase II trial.
There was considerable anticipation this summer when the latest trial began, combining two immunotherapy drugs that had shown reasonable success individually with mesothelioma patients.
CRS-207 uses a genetically engineered listeria virus to produce an immune response to a specific tumor antigen.
In one previous study of CRS-207 alone, an estimated 30 percent of the patients experienced mesothelioma tumor shrinkage. A combination of CRS-207 with chemotherapy produced tumor shrinkage in 85 percent of the patients and with a 35 percent disease control rate.
In a previous study of Keytruda, more than 50 percent of mesothelioma patients experienced initial tumor reduction.
The pretrial hope was a synergy effect between the drugs might produce a significant advancement in treatment.
Unfortunately, it wasn’t happening, according to Aduro executives.
“While the biomarker data demonstrated activation of innate and adapted immunity, there is a lack of compelling clinical activity,” said Dr. Natalie Sacks, Aduro chief medical officer. “We had hoped to share encouraging preliminary results from the ongoing studies, but unfortunately, based on the initial patients treated, the data does not support continued advancement of CRS-207.”
Financial Decisions with Drug Development
Although optimism regarding CRS-207 and mesothelioma had been building with earlier trials, it wasn’t without setbacks.
The FDA in 2016 stopped all clinical trials temporarily over listeria infection concerns. The trials resumed, though, after protocols were modified.
Aduro executives said safety of the drug was not an issue in dropping the CRS-207 project for mesothelioma and ovarian cancers.
The decision, in part, was a desire to move company funds and various resources to other ongoing drug development projects, according to Isaacs.
The trial was designed for a second-line setting, helping patients whose disease had progressed after standard-of-care treatment.
“The discipline to make this decision is important,” Isaacs said. “We took a look at business considerations, clinical considerations, marketing considerations, and enrollment considerations, and came to the conclusion that this is the best things to do at this point and time.”