City of Hope cancer center thoracic oncologist Dr. Marianna Koczywas explains the workings of tazemetostat — the latest drug tested in a mesothelioma clinical trial — with the lock and key metaphor.
“You have a specific [cancer] key, and a specific keyhole it goes through. If you can lock that keyhole, you can lock it out,” Koczywas told Asbestos.com. “These malignant cells rely on a pathway for growth and division so you try and block that specific pathway.”
Koczywas is principal investigator for the mesothelioma clinical trial at the City of Hope National Medical Center in Los Angeles, one of eight locations in the U.S. recruiting patients for this promising phase II trial.
The other cancer centers hosting the clinical trial include:
Several centers in the U.K. and France are also hosting the trial.
“We’re opening this trial because we believe it is promising,” Koczywas said. “We still have very limited options for patients with mesothelioma and welcome any therapy with potential to benefit the patients, prolong life and provide better quality of life. We think this drug can do that.”
Tazemetostat, a small-molecule protein inhibitor, already showed effectiveness in treating non-Hodgkin lymphoma, synovial sarcoma and certain genetically defined solid tumors. All use a similar pathway to tumor cell proliferation.
Earlier studies have shown a mutation of BAP1, the tumor suppressor gene, in 60 percent of mesothelioma cases. Tazemetostat has shown effectiveness for that mutation in other cancers.
Earlier research revealed people lacking the BAP1 protein are more likely to develop malignant mesothelioma, but the mutation gives them a better chance with therapy.
“Having this type of personalized and targeted therapy for patients is the way of the future,” Koczywas said. “You will see a higher response rate and a longer benefit by designing very specific, targeted therapies. We can select patients better today.”
Epizyme Inc., a clinical-stage biopharmaceutical company creating novel therapies for cancer, produces tazemetostat.
“We believe that tazemetostat has the potential to treat multiple types of cancer in patients who have limited treatment options,” Epizyme president and CEO Robert Bazemore said in a press release. “We are moving quickly to expand the tazemetostat clinical program into mesothelioma.”
The drugmaker is promoting tazemetostat as a second-line therapy for those already treated with chemotherapy but who relapsed. Standard-of-care treatment typically includes a combination of surgery, radiation and chemotherapy.
Mesothelioma is a rare and aggressive cancer caused typically by a prolonged, occupational exposure to asbestos. There currently is no FDA-approved second-line therapy for the cancer, which leaves a void tazemetostat could possibly fill.
The trial, which started last month, is expected to run through September 2018. Treatment, which is administered orally, will continue until disease progression or unacceptable toxicity.
“Cancer types that rely on this pathway seem to be responding to the drug,” Koczywas said. “This therapy should be appealing to patients who have very few options.”
Clinical trials offer no guarantees, but they often serve as the best hope for patients with mesothelioma, providing the latest treatments moving toward U.S. Food and Drug Administration approval. They play an essential role in developing new therapies.
“Participating in clinical trials is crucial to advancing cancer treatment in general, and maybe moving us closer to a cure,” Koczywas said. “We encourage patients to take a look. And we thank those who participate.”