The U.S. Food and Drug Administration has granted accelerated approval to Keytruda (pembrolizumab) for the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL), making it the first anti-PD-1 therapy approved in the U.S. for this type of cancer.
The conditional accelerated approval is for adults and children who failed to respond or progressed after two or more prior lines of therapy, and is contingent upon additional results demonstrating Keytruda’s effectiveness.
Merck’s Keytruda is an anti-PD-1 therapy that works by increasing the immune system’s ability to detect and fight tumor cells. This is the second time Keytruda has been approved for the treatment of a blood malignancy.
The new indication was approved under the FDA’s accelerated approval program, based on tumor response rate and durability of response achieved in the KEYNOTE-170 Phase 2 clinical trial (NCT02576990).
“Relapsed or refractory PMBCL is often a challenging disease to treat, and many affected patients are young adults,” Philippe Armand, an MD and PhD, medical oncologist at Dana-Farber Cancer Institute, said in a press release.
“In the clinical trial that supported this approval, treatment with Keytruda resulted in meaningful responses, including complete disease remission in some patients,” he said. “This approval therefore provides another therapeutic option for patients with PMBCL who have progressed on or after prior therapies.”
KEYNOTE-170 is a multicenter, open-label, single-arm trial that is currently evaluating Keytruda in 53 patients with relapsed or refractory PMBCL. Patients received 200 mg Keytruda every three weeks until unacceptable toxicity or disease progression, or up to 24 months for patients whose disease didn’t worsen.
Effectiveness was determined through overall response rate and duration of response, but researchers will also assess the time a patient lives without disease worsening, overall survival, and overall safety.
Patients in the KEYNOTE-170 trial range from ages 20-61, with 43 percent male and 92 percent white. On average, participants had received at least three prior lines of therapy.
Overall, 45 percent of patients experienced a significant reduction of their tumors, with 11 percent achieving a complete response. More than half of these 24 patients are still responding to treatment. For these patients, the median time to first objective response (complete or partial) was 2.8 months, ranging between 2.1 and 8.5 months.
Efficacy for pediatric patients with PMBCL was extrapolated from the results among the adult PMBCL patients and crossed with findings from another study of 40 pediatric patients who were given Keytruda at 2 mg per kg body weight every three weeks.
Keytruda’s safety profile in these children was similar to that seen in adults; however, toxicities occurred at higher rates.
“The approval of our anti-PD-1 therapy, Keytruda, for the treatment of refractory or relapsed PMBCL provides an important therapeutic option for patients who have this rare disease,” said Jonathan Cheng, MD, vice president of oncology clinical research at Merck Research Laboratories.
“This approval reinforces Merck’s commitment to helping patients diagnosed with hematologic cancers and marks the second indication for Keytruda in a hematologic malignancy,” he said.
The FDA agreed to review Merck’s application in December 2017. At the time, the application had already been supported by data from KEYNOTE-170, which researchers presented in December at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta.
For this review, the regulatory agency also considered data from the Phase 1b KEYNOTE-013 clinical trial (NCT01953692), a study of Keytruda in various blood cancers that included PMBCL patients.
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