In an unprecedented, fast-tracked review, FDA granted accelerated approval to a treatment for patients whose cancers have a specific genetic feature.
This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.
Keytruda (pembrolizumab) is sponsored by Merck & Co.
The drug’s most recent indication is for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient.
This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.
“This is an important first for the cancer community,” said Richard Pazdur, acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”
MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places. Approximately 5 percent of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.
Keytruda was approved for this new indication using the accelerated approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients.
Further study is required to verify and describe anticipated clinical benefits of Keytruda, and the sponsor is currently conducting these studies in additional patients with MSI-H or dMMR tumors.
The safety and efficacy of Keytruda for this indication were studied in patients with MSI-H or dMMR solid tumors enrolled in one of five uncontrolled, single-arm clinical trials. In some trials, patients were required to have MSI-H or dMMR cancers, while in other trials, a subgroup of patients were identified as having MSI-H or dMMR cancers by testing tumor samples after treatment began.
A total of 15 cancer types were identified among 149 patients enrolled across these five clinical trials. The most common cancers were colorectal, endometrial and other gastrointestinal cancers. The review of Keytruda for this indication was based on the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and for how long (durability of response).
Of the 149 patients who received Keytruda in the trials, 39.6 percent had a complete or partial response. For 78 percent of those patients, the response lasted for six months or more.
Bert Vogelstein, co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center and a Lustgarten Foundation Distinguished Scholar who helped direct this study, described the therapy as “the first example of ‘personalized immunotherapy.’ A specific immune treatment can now be recommended for patients based exclusively on the genetic characteristics of their tumor. If the tumor shows a repair defect, then it is very likely that it will respond to this drug, regardless of how advanced the cancer is at the time of treatment.”
It is estimated that approximately 1 in 50 advanced pancreatic cancer patients have MMR in their tumors that make them candidates for this type of therapy.
The study was conducted at the Johns Hopkins Bloomberg-Kimmel Institute, funded in part by the Lustgarten Foundation, “This is an incredibly important step forward and we are delighted to have had a key role in its success,” said David Tuveson, director of Research for the Lustgarten Foundation. “Patients have responded very well to this drug. This is the beginning of personalized medicine for pancreatic cancer patients.”