Keytruda (pembrolizumab) is a monoclonal antibody developed by Merck that blocks the interaction between the PD-1 receptor and its ligands, increasing the body’s ability to activate immune cells to fight cancer.
PD-1 is a protein that prevents T-cells from being overly aggressive and attacking healthy cells. By blocking PD-1, Keytruda increases the immune system’s responsiveness, and its ability to take on tumor cells. The drug works to unleash T-cells so that they can destroy melanoma cells anywhere in the body. (But in removing an immune system check, Keytruda can also unleash T-cells that damage normal cells.)
The U.S. Food and Drug Administration (FDA) approved Keytruda in 2014 to treat patients with advanced or unresectable melanoma who are no longer responding to other drugs. Then in 2015, based on results of a pivotal Phase 3 trial, the FDA decided to expand Keytruda to be a first-line treatment of patients with advanced melanoma. The drug is now approved for melanoma patients with Stage III disease that is unresectable (unable to be completely removed by surgery), and those with Stage IV disease, or metastatic cancer, regardless of BRAF status.
It is administered intravenously, and each dose takes about 30 minutes to complete. Patients usually receive the drug every three weeks, unless their melanoma worsens or they experience side effects. There is no need for a hospital stay.
Keytruda studies
The approval of Keytruda for melanoma was based on clinical trials that assessed its safety and efficacy both as a monotherapy and in combination with other drugs.
In a Phase 3 clinical trial (KEYNOTE-006; NCT01866319) Keytruda was found to offer superior overall survival rates in advanced melanoma patients compared to another checkpoint inhibitor, Yervoy (ipilimumab). The study randomized 834 patients to receive Keytruda at 10 mg/kg every three weeks (277 people), Keytruda 10 mg/kg every two weeks (279 people), or four cycles of Yervoy 3 mg/kg every three weeks (278 people). In this study supporting approval as a first-line treatment, patients given Keytruda every two weeks had a 37 percent reduction in the risk of death and those treated every three weeks a 31 percent reduction, both compared to Yervoy. Keytruda was also seen to reduce the risk of disease progression by 42 percent in people treated every three weeks.
To evaluate whether the combination of Keytruda and a reduced-dose of Yervoy could induce robust responses with less toxicity, an open-label Phase 1/2 clinical trial (KEYNOTE-029; NCT02089685) was undertaken. A total of 153 patients with advanced melanoma and no brain metastasis, who had not received any prior immunotherapy, were enrolled. Patients received four doses of Keytruda (at 2 mg/kg) and Yervoy (at 1 mg/kg) every three weeks, followed by Keytruda monotherapy for up to 24 months (or until disease progression or unacceptable toxicity). Results presented in October 2016 at the American Society of Clinical Oncology (ASCO) annual meeting, showed the combination offered potent anti-tumor activity with acceptable toxicity.
In an ongoing Phase 2 trial (NCT02681549), Keytruda has shown therapeutic effects in brain metastases in patients when combined with Avastin (bevacizumab). The study is being conducted in patients with melanoma and non-small cell lung cancer (NSCLC). In this trial 36 patients with melanoma or NSCLC with untreated brain metastases are being given 10 mg/kg of Keytruda intravenously every two weeks, in addition to Avastin.
Early results reported in August 2016 showed that 22 percent of melanoma patients and 33 percent of NSCLC patients had a brain metastasis response following treatment. There were some neurological effects associated with the treatment, however, and six melanoma patients and nine NSCLC patients died of disease progression. The study, which is taking place in Connecticut and still recruiting, is expected to end in May 2019.
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