FDA Grants Unique Approval for Cancer Drug Keytruda

Posted May 25, 2017

On May 23, the US Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab, made by Merck and marketed as Keytruda, for adults and children without remaining treatment alternatives and with metastatic solid tumors identified with a biomarker called microsatellite instability-high (MSI-H) or mismatch fix deficient (dMMR).

The drug, a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, thereby activating T lymphocytes, is already approved in the United States for indications within melanoma, lung cancer, head and neck cancer and classical Hodgkin lymphoma (cHL). Merck announced May 18 that the U.S. Food and Drug Administration (FDA) granted Keytruda two approvals for bladder cancer, MarketWatch reported.

"It is the first pan-cancer biomarker in the history of cancer treatment that defines or identifies patients that will benefit from a particular form of therapy regardless of the tissue of origin of the cancer", Drew Pardoll, director of the Johns Hopkins Bloomberg~Kimmel Institute and a collaborator of the Phase 2 trial testing Keytruda in this indication, told BioPharma Dive in an interview.

Keytruda belongs to a new class of drugs called PD-1 or PD-L1 inhibitors that block a mechanism tumors use to evade detection from cancer-fighting cells.

The accelerated FDA approval was intended for solid tumor cancers no longer fit for surgeries or have metastasized or spread in those identified with a biomarker known as microsatellite instability-high (MSI-H) or mismatch fix deficient (dMMR).

"Nearly 100,000 people are living with gastric cancer in the United States, yet little progress has been made in bringing forward new treatment options to these patients for whom chemotherapy has always been the standard of care", Roger D. Dansey, MD, senior vice president and therapeutic area head for oncology late-stage development at Merck Research Laboratories, said in a company-issued press release. The ORR was similar among patients diagnosed with colorectal cancer, 36%, or 1 of the 14 other cancer types, 46%. Of those patients, 78% had a response that lasted for 6 months or longer.

"This is an important first for the cancer community", said Richard Pazdur, of the FDA's Center for Drug Evaluation and Research in a statement.

MSI-high or MMR-deficient tumors are most commonly found in endometrial cancer, colorectal cancer (up to 5% of metastatic patients), and other gastrointestinal cancers.

Common side effects include fatigue, itchy skin, diarrhea, rash, decreased appetite, fever, cough, dyspnea or difficulty breathing, nausea, muscle and joint pain, and constipation.

In the initial studies nearly 40% of patients saw a partial or complete response with Keytruda at a fixed dose of 200mg every three weeks, and in 78% of them the effect lasted for at least six months.

Merck has been granted accelerated approval for Keytruda in this indication based on the results of five uncontrolled single-arm clinical trials involving 149 patients, so it will have to provide additional evidence of the drug's efficacy in further studies if it is to keep the indication on the label.

Merck's Keytruda, which works by harnessing the body's immune system to attack tumors, has previously been approved to treat several site-specific tumors, including those of the skin and lung.

According to Pardoll, around 4 percent of advanced cancer cases, or up to 20,000 US cases every year, have the genetic features involved in the FDA approval. MSI-H is already an established biomarker in certain types of cancer.