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FDA Approves Merck’s Keytruda (Ab to PD-1) for Treatment of Advanced Non-Small-Cell Lung Cancer (85% of All Lung Cancer); Companion Test to ID Patients Most Likely to Benefit Also Approved

Pembrolizumab (trade name Keytruda), a drug that has already been proven to extend the lives of people with advanced melanoma, was approved on October 2, 2015 by the U.S. Food and Drug Administration (FDA) to treat advanced non-small-cell lung cancer (NSCLC) in patients whose tumors express the protein PD-L1 (programmed cell death ligand 1). Keytruda is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, which is the first test designed to detect PD-L1 expression in NSCLC. Keytruda is marketed by Merck & Co., based in Whitehouse Station, New Jersey, and the PD-L1 IHC 22C3 pharmDx diagnostic test is marketed by Dako North America Inc. in Carpinteria, California. Richard Pazdur, M.D., Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said that the “approval of Keytruda gives physicians the ability to target specific patients who may be most likely to benefit from this drug.” The clinical trial study of Keytruda in advanced NSCLC represents the largest published research to date using immunotherapy to treat lung cancer, and the trial was conducted at UCLA and 29 other sites in the U.S., Europe, and Australia. “The approval of this drug and a test to identify patients most likely to benefit has the potential to transform the way that lung cancer is treated,” said Dr. Edward Garon, the study’s principal investigator and a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “The quality and duration of disease response that was seen in the trial had previously been extremely rare in lung cancer. For people battling this deadly disease, this approach provides real hope of long-lasting responses while avoiding the toxicities of typical chemotherapy.” The drug, which is marketed under the brand name Keytruda, was tested on approximately 500 patients with NSCLC. Because so many of the patients in the study showed significant long-lasting responses, in October 2014, the FDA granted the drug “breakthrough therapy” status for use in lung cancer, allowing it to be fast-tracked for approval. Keytruda is an antibody that targets the protein PD-1 (programmed cell death 1), which is expressed by immune cells. When PD-1 binds to another protein called PD-L1 (programmed cell death ligand 1), PD-1 acts as an immune checkpoint, dampening the activity of the immune system’s T cells, which otherwise could attack cancer cells, said Dr. Garon, who also is an Associate Professor of Hematology-Oncology at the David Geffen School of Medicine at UCLA.

Some tumors are able to evade an immune response by expressing high levels of PD-L1. So, by blocking the interaction between PD-1 and PD-L1, Keytruda, in effect, enables the patient’s immune system to attack the cancer.

The response rate and duration of response for Keytruda were much greater than for drugs traditionally used to treat lung cancer. In the three-year clinical trial, the overall response rate (the percentage of people in whom tumors were substantially reduced in size) was 19 percent. In people who responded to treatment, the average duration of response exceeded one year, considered a remarkable advance in this difficult disease.

Approximately a quarter of patients in the trial had PD-L1 expression in at least half of their tumor cells. Among these patients, the overall response rate was nearly 50 percent. Although previous data suggested that clinical outcomes with this class of drugs may be associated with level of PD-L1 expression, this study is the first to validate this finding in the scientifically rigorous way that physicians and scientist generally demand.

The study has now led to the approval of Keytruda for treating two diseases, lung cancer and melanoma, as well as the approval of a diagnostic test for PD-L1 to select the lung cancer patients who are most likely to benefit.
Judith Gasson, Ph.D., Director of the Jonsson Cancer Center and Senior Associate Dean for Research at the David Geffen School of Medicine at UCLA, said researchers have long hoped to develop an effective and lasting immunotherapy to fight cancer.

“We have long believed that harnessing the power of our own immune systems would dramatically alter cancer treatment,” she said. “Based upon the pioneering work conducted at UCLA, we are beginning to see the clinical benefits of this research in the most challenging cancers.”

Lung cancer is the leading cause of cancer deaths worldwide; the American Lung Association estimates that more than 158,000 people in the U.S. will die from the disease this year alone. NSCLC accounts for approximately 85 percent of all lung cancers.

Further research into Keytruda’s possible use to treat other types of cancer is ongoing, as are efforts to combine Keytruda with other drugs to increase the number of patients who could benefit from immunotherapy.


For Cary Parton, 61, life now has an entirely new meaning following a late-stage cancer diagnosis in which doctors told Parton that he had only months to live.

In February 2013, he was swinging a golf club on a fairway in Palm Springs, California, when he felt a sharp pain in the middle of his back. After a month, Parton was in such bad shape that he could hardly get out of bed, and his wife took him to the hospital.

After Parton underwent a full medical examination and a CT scan, doctors discovered a form of NSCLC that had spread all over his body.

“The biggest tumor was on my right lung, and more were found on my liver, adrenal gland, two lymph glands, on my spine, and both sides of my sacrum,” Parton said.

Although Parton had been a smoker, he had quit several years before his cancer diagnosis. His oncologist at the time had recommended traditional treatment, which included radiation and chemotherapy for nearly two months. But the cancer only worsened, and, at that point, after talking with friends and family, Parton decided to enroll in an immunotherapy clinical trial at UCLA conducted by Dr. Garon.

Parton started taking Keytruda in June 2013, and, within 10 weeks, his tumors had shown a reduction of 40 percent. Another two and a half months later, scans showed additional reductions, and by February 2014, they had been reduced by 86 percent. As of today, Parton’s tumors have shrunk by more than 95 percent.

“Keytruda was a life saver,” Parton said. “To see me alive today is pretty miraculous. It’s astounding.”

[UCLA press release] [FDA press release] [Eureka Alert press release]

[Wall Street Journal articlet] [U.S. News & World Report article] [Reuters article]