Yale Cancer Center director led trials for FDA-approved drug

A drug whose clinical testing was led by Charles S. Fuchs, M.D., M.P.H., Richard Sackler and Jonathan Sackler Professor of Medicine (Medical Oncology) and director of Yale Cancer Center, has become the first approved immunotherapy treatment for advanced stomach cancer.

The drug, pembrolizumab (Keytruda^®), was approved by the U.S. Food and Drug Administration (FDA) for adult patients diagnosed with advanced stomach cancer or gastroesophageal junction cancer showing PD-L1 positive tumors, in cases where the cancer has progressed despite two or more prior lines of treatment with standard therapies. Pembrolizumab works by increasing the ability of the body’s immune system to help detect and fight tumor cells.

The FDA made its approval on an accelerated basis, deciding to forego Phase III clinical trials after a Fuchs-led Phase II trial of pembrolizumab had demonstrated the value of the drug for patients with the PD-L1 mutation.

Persuasive data from the trial, called KEYNOTE-059, were presented last September at the European Society for Medical Oncology (ESMO) annual meeting. Sixteen percent of PD-L1-positive patients had achieved at least a partial response to the treatment, including several patients whose tumors completely disappeared. Some of those responses lasted for what were considered long periods of time, ranging from several months to more than a year.

“The responses really are quite robust and far longer than you would see with any cytotoxic chemotherapy agent,” says Fuchs.

Prior to pembrolizumab, the only FDA-approved drug for non-responsive stomach cancer was ramucirumab (Cyramza^®), a monoclonal antibody whose benefits to patients have been classified as “modest” by the National Cancer Institute.

Fuchs says progress against advanced stomach cancer has been less robust than he would like because very few drugs have been developed to address the particular biology of the cancer. “Most commonly,” he explains, “we use anticancer drugs that are used to treat other cancers and apply them to patients with stomach cancer because we just don’t have dedicated efforts to develop drugs specific for stomach cancer.” That is a deficit he hopes to continue to rectify.