Keytruda (pembrolizumab) is a prescription medicine developed by Merck to treat cancers — both blood cancers and solid tumors — that have spread, relapsed, or are unresponsive to therapy. Keytruda may be used as a treatment for classical Hodgkin lymphoma (cHL), melanoma, non-small cell lung cancer (NSCLC), and head and neck squamous cell cancer (HNSCC).
The drug was granted accelerated approved in March 2017 by the U.S. Food and Drug Administration (FDA) for cHL in adults and children when other treatments did not work or when the cancer returned after three or more types of treatments. Keytruda has also been approved by the European Commission as a treatment for cHL.
In May 2017, the FDA granted accelerated approval to Keytruda for people whose cancers have the same specific genetic biomarker, or feature; these biomarkers are most often found in colorectal, endometrial and gastrointestinal cancers. This marked the first time that the FDA approved a cancer treatment based on a common biomarker instead of the location in the body where the tumor started.
Keytruda was approved by the FDA to treat other cancers, like melanoma and NSCLC, earlier.
How Keytruda works
Keytruda is an anti-PD-1 (programmed death receptor-1) blocker, which works by disturbing the normal function of the immune system to activate inflammation and promote cancer cell death.
PD-1, also known as CD 279 (cluster of differentiation 279), is a receptor molecule that exists on the surface of immune cells. When activated by its ligands (PD-L1 and PD-L2), it prevents the immune system from attacking healthy cells (also known as autoimmunity) by suppressing the function of specialized immune cells called T-cells, which generate inflammation. When bound to its ligand, the receptor also adjusts the action of regulatory, anti-inflammatory T-cells.
Keytruda is a monoclonal antibody that binds to PD-1, blocking the interaction between PD-1 and its ligands. This results in a higher activation of inflammatory T-cells and increases the ability of the body’s immune system to help detect and fight tumor cells.
Studies with Keytruda
Keytruda is currently being tested in a multicenter, open-label study to assess its safety and efficacy to treat cHL patients who failed or were ineligible for stem cell transplant and for patients who did not receive Adcetris (brentuximab vedotin) treatment or for whom this treatment failed.
A Phase 2 clinical trial called KEYNOTE-087 (NCT02453594), which is still ongoing, enrolled 210 patients with relapsed/refractory cHL, who had received at least three previous lines of therapy. Patients in the open-label trial (no placebo group) received 200 mg of Keytruda every three weeks until unacceptable toxicity or disease progression.
Interim results, on which the FDA based its March accelerated approval, showed that after a median 9.4 months of follow-up, the overall response rate was 69 percent, with 22 percent of participants achieving complete remission and 47 percent achieving partial remission. The median duration of response was 11.1 months.
In a Phase 1b clinical trial called KEYNOTE-013 (NCT01953692), currently recruiting patients in the U.S. and Europe, patients with various types of lymphoma are receiving Keytruda every two weeks at a dose of 10 mg/kg. Following a median follow-up time of 28.7 months, 58 percent of patients had responded to the treatment, with 19 percent achieving complete remission and 39 percent partial remission.
There is limited experience with Keytruda in children, but in the Phase 1/2 KEYNOTE-051 study (NCT02332668) that is currently recruiting participants, 40 children, ages six months to 17 years, with advanced melanoma, PD-L1-positive advanced, relapsed, or refractory solid tumors, or lymphoma are being treated with Keytruda for a median of 43 days. Of these, 24 patients received treatment for 42 days or more. No results have yet been published for this study, which is set to conclude in early 2019.
The most common adverse reactions (greater than 10 percent) seen in clinical trials with Keytruda were fatigue (22 percent of patients), pruritus (15 percent of patients), rash (13 percent), diarrhea (12 percent), and nausea (10 percent). The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.
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