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BioCentury – FDA, NCI study will serve as prototype for streamlined pragmatic trials

BioCentury – FDA, NCI study will serve as prototype for streamlined pragmatic trials

Two U.S. government agencies, two pharmaceutical companies and an academic cooperative trials group are collaborating to conduct a pragmatic clinical trial of a combination therapy for advanced non-small cell lung cancer. They hope the trial, which FDA has dubbed Project Pragmatica, will be a model for quickly answering urgent questions that can shape clinical practice.

Richard Pazdur, director of FDA’s Oncology Center of Excellence, and NCI Director Monica Bertagnolli described the origins and goals of Project Pragmatica Thursday at the Friends of Cancer Research annual meeting.

The idea for the project “came to me like a lightning bolt,” Pazdur said, when he was reviewing results of a Phase II trial conducted as part of the Lung-MAP master protocol. In the trial, a combination of Cyramza ramucirumab from Eli Lilly and Co. (NYSE:LLY) and Keytruda pembrolizumab from Merck & Co. Inc. (NYSE:MRK) produced a survival benefit in patients with advanced NSCLC who had received at least one line of anti–PD-1 or anti–PD-L1 therapy for stage III, IV, or recurrent disease as well as platinum-based chemotherapy.

Although the results were potentially important, the trial was not designed as a registration trial and it could not support an approval, Pazdur said.

Thinking about the fastest way to obtain data that could support an approval decision, Pazdur said he realized that “I’m only interested in one thing,” whether the drugs produce an overall survival benefit. Both drugs have been widely used, so there is no need to study their safety, he added.

FDA worked with researchers at NCI, the SWOG Cancer Research Network, and Merck and Lilly to design a trial with a single endpoint, overall survival. Any NSCLC patient whose disease has progressed after treatment with an immunotherapy and standard chemotherapy will be eligible to participate. Patients will be randomized to the two-drug combination or the treating physician’s choice of chemotherapy.

NCI is providing most of the funding for the trial. Merck and Lilly are providing drugs and some financial support.

The Lung-MAP trial results produced a signal, “but we need to know more,” Bertagnolli said at the Friends meeting. “We need to know whether a two-drug combination can really benefit patients with recurrent or advanced lung cancer.”

She emphasized the streamlined nature of the trial, which will not include the extensive set of secondary endpoints that are typical in cancer trials, as well as the speed with which it is has gone from concept to reality.

NCI, the Lung-MAP team, FDA and the Foundation for NIH started designing the trial in July, the protocol was submitted to a central IRB on Nov. 17, and enrollment of the first patients is slated for January, Bertagnolli reported.

She emphasized the role of Merck and Lilly in facilitating the trial. “Our industry partners stepped up.”

Bertagnolli, who recently took on the job of running NCI, said Project Pragmatica is a prototype for the kind of trials and public-private collaboration she plans to pursue.

NCI and FDA are already discussing collaboration on additional pragmatic cancer trials, an FDA official told BioCentury.