By Jo Cavallo August 10, Advertisement. The FDA granted accelerated approval for this new indication of pembrolizumab based on results from five uncontrolled, single-arm clinical trials. In some of these trials, patients were required to have MSI-H— or dMMR-based cancers, and in other trials, a subgroup of patients were identified as having MSI-H cancers by testing tumor samples after treatment began.
A total of 15 cancer types were identified among the patients enrolled across the 5 clinical trials. The most common were colorectal, endometrial, and other gastrointestinal cancers. Of the patients who received pembrolizumab in these studies, How significant a change in the FDA drug evaluation process is the approval of pembrolizumab as the first tumor-agnostic agent in the treatment of solid tumors?
This new indication represents a shift in our evaluation of therapies. The approval moves us away from the strict disease-site indication, such as breast, colon, or lung cancer, to a site-agnostic indication. It changes how we may define cancer—the disease is no longer being solely determined by its site of origin or pathologic diagnosis. It is now defined by Site agnostic presence of a specific biomarker. When we heard about patients Site agnostic refractory colon cancer, cholangiocarcinomas, endometrial carcinomas, esophageal carcinomas, and small bowel cancers and observed clinically meaningful responses to pembrolizumab with substantial Site agnostic, we worked proactively with the drug sponsor to develop this new indication.
These patients had either largely ineffective treatment options or no options available. I put myself in the position of a potential patient. If I had one of these cancers and had exhausted all therapies, I would want my tumor tested for this biomarker.
And if it was positive, I certainly would want this Site agnostic because, while not all patients responded to this therapy, those who did experienced obvious benefit. Small numbers of patients were enrolled in these clinical trials, and there are overlapping confidence intervals surrounding the point estimates of the response rates. I cannot make the statement that we would have seen a differential response based on tumor location.
We are open to "Site agnostic" with drug sponsors on site-agnostic indications based on a strong scientific rationale and robust clinical results.
We also consider whether other effective therapies are available. Patients entered on the pembrolizumab clinical trials had few or no satisfactory available options. If a situation exists where there is effective therapy available, a randomized trial may be Site agnostic to determine the benefit of the new drug against the existing therapy. That was not the situation for this approval. The new indication clearly states that pembrolizumab was given accelerated approval for patients with solid tumors that had progressed following prior treatment and for whom there were no satisfactory alternative treatment options.
Unlike other accelerated drug approvals, we did not ask for a randomized study to be performed as a postmarketing requirement.
This request would not have been feasible due to the small of patients as well as the lack of a reasonable standard treatment. Alternatively, we requested that more data be collected in different cancer types with the MSI-H biomarker.
Pembrolizumab had already been approved in the advanced setting for Site agnostic treatment of several cancers. Some drugs targeting tumor-driving gene defects do not work universally.
How will approval for site-agnostic drugs change the way cancer is treated? There is not a one-stop solution for every clinical situation. For a drug directed toward a specific biomarker, the level of activity and benefit may depend on the disease site. We then put this information into the context of existing therapies for the given patient population. How is the Center changing the way cancer drugs and Site agnostic products are approved?
The leverages the combined skills of the scientists and reviewers at the FDA with expertise in drugs, biologics, and medical devices under one regulatory umbrella. It facilitates an active exchange among the various centers and offices across the agency, including the Center for Drug Evaluation and Research, the Center for Biologics Evaluation Research, and the Center for Devices and Radiological Health. We have launched several scientific programs, are engaged in collaborative reviews of drugs and devices Site agnostic the centers, and have many more meetings to interact with the centers to discuss products.
This provides us with an integrated approach in the clinical evaluation of oncology therapies. The ultimate goal of the OCE is to expedite the development of oncology and hematology therapies and medical devices, to provide patients with cancer more and Site agnostic treatment options. New and Important Changes Howard M.
This is the FDA's first tissue/site-agnostic approval. The approval was based on data from patients with MSI-H or dMMR cancers enrolled.
Approval of pembrolizumab (MSI. H/dMMR) and considerations for site-agnostic development of drugs in oncology.