Tag Archives: yervoy

Merck melanoma drug shrinks tumors in 38 percent of patients

A Merck & Co drug designed to unmask tumor cells and mobilize the immune system into fighting cancer helped shrink tumors in 38 percent of patients with advanced melanoma in an early-stage study, U.S. researchers said on Sunday. Based on the findings about the drug lambrolizumab, published in the New England Journal of Medicine and presented at the American Society of Clinical Oncology meeting in Chicago, Merck says it will move directly into a late-stage clinical trial, which will start in the third quarter. “This is a top priority at Merck,” Dr. Gary Gilliand, senior vice present and head of oncology at Merck Research Laboratories said in a meeting with investors. “We're going flat out to deliver benefit to patients with this novel mechanism.” The moves may heap pressure on market leader Bristol-Myers Squibb, maker of Yervoy - the only approved immune system drug for the treatment of advanced melanoma, the deadliest form of skin cancer. Bristol-Myers is conducting three phase-three studies of its own drug called nivolumab in advanced melanoma, and is studying the drug's effect on a range of other cancers, including lung cancer. Both nivolumab and lambrolizumab are part of a promising new class of drugs that disable programmed death 1 or PD-1, a protein that keeps the immune system from spotting and attacking cancer cells. “Even though it's (lambrolizumab) the second player in the field and even though it's all early, it impressed me,” said Dr. Antoni Ribas of the University of California Los Angeles' Jonsson Comprehensive Cancer Center, the lead author of the study. Last month, the U.S. Food and Drug Administration deemed the treatment a “breakthrough therapy,” a designation FDA cancer drugs chief Dr. Richard Pazdur described as “knock-your-socks-off therapies.” Results of an early-stage study of nivolumab in advanced melanoma released at the cancer meeting showed 31 percent of patients overall responded to different doses of the drug. Among those who took the 3 milligram per kilogram dose, 41 percent of patients responded. The drug response lasted an average of two years, and in many patients the drug kept working even after they stopped taking it. Analysts expect the drugs to generate billions of dollars in sales. Nivolumab alone is forecast to have sales of $1.2 billion in 2017, according to Wall Street analysts tracked by Thomson Reuters Pharma. Merck's study Merck's results are from the first clinical trial of lambrolizumab in advanced melanoma. They are based on analysis of 135 patients with metastatic melanoma who were divided into three groups with different treatment regimens. Overall, lambrolizumab resulted in 38 percent of patients having confirmed improvement of their cancer across all dose levels given after 12 weeks of treatment. But there was a wide range among doses, with only a 25 percent rate among patients who got the lowest dose and 52 percent among those who got the highest dose. In the highest dose group, 10 percent had a complete response, meaning their tumors could not be detected on scans. Side effects were generally mild and included fatigue, fevers, skin rash, loss of skin color and muscle weakness. More severe side effects were seen in 13 percent of patients, including inflammation of the lung or kidney and thyroid problems. “This study is showing the highest rate of durable melanoma responses of any drug we have tested thus far in this cancer, and it is doing it without serious side effects in the great majority of patients,” Ribas said. Merck said it plans to start a late-stage randomized trial of the drug in melanoma and in non-small cell lung cancer in the third quarter of this year. The company recently started a global, randomized mid-stage study of the drug versus standard chemotherapy in patients whose disease had progressed. And it is studying the drug as a treatment for triple negative breast, metastatic bladder and head and neck cancers. Researchers at the meeting marveled at responses to new immune system treatments after decades of failed studies among patients with melanoma. Only about one in five patients respond to Yervoy, approved in 2011 as the first immunotherapy to extend survival in patients with advanced melanoma. Yervoy works by blocking CTLA-4, a different molecule that also keeps the immune system from attacking cancer. Ribas said he has followed one patient on Yervoy for 12 years now. “She's not supposed to be around, and she's alive and well and melanoma free. That is why we've been doing these immunotherapies,” he said. With Yervoy, Ribas said these types of responses were few and far between. With the new PD-1 drugs, they are much more common, with fewer side effects. However, an early-stage Bristol-Myers' study released this month showed that 53 percent of patients who got a combination of Yervoy and nivolumab had at least a 50 percent reduction in tumor size, with fewer side effects. Tim Turnham, executive director of the Melanoma Research Foundation, said combination treatments would make a major difference for patients because they help overcome cancer's “sneaky” ability to evade treatment. But, at this point, he said, “Nobody knows which one is better.”source : http://www.foxnews.com/health/2013/06/03/merck-melanoma-drug-shrinks-tumors-in-38-percent-patients/

Immunotherapy now used to treat cancers beyond melanoma

Diagnosed with advanced lung cancer over a year ago, Gabe Tartaglia was loath to undergo the kind of harsh chemotherapy that had devastated his sister before her death three years earlier from pancreatic cancer. He decided to enter a clinical trial for a new drug designed to trigger the immune system to fight cancer. The results were better than anyone expected. “Everything has shrunk,” said the 62-year-old contractor from Wolcott, Connecticut, who still goes for treatment every two weeks and has regular scans to keep tabs on his progress. “Some of the tumors you can't even see.” Just a few years ago, nobody believed it was possible to harness the immune system to respond to cancer, but drugs like nivolumab, the experimental Bristol-Myers drug Tartaglia receives, are showing promise, even in some patients who have never tried any other treatments. The drugs will be a main focus of this year's American Society of Clinical Oncology five-day meeting in Chicago beginning on May 31. Much of the attention will be trained on agents that disable a protein called programmed death 1, or PD-1, that enables tumors to evade the immune system. In addition to nivolumab, experimental drugs in the class include Merck's lambrolizumab and Roche's MPDL3280A, which work by blocking a partner protein known as PD-L1 (the L is for ligand). PD-L1 in turn works within cancer cells to shut down the immune response. Analysts and investors will be parsing the ASCO data for clues to the market potential for the drugs, which are expected to generate billions of dollars in annual sales. Nivolumab alone is forecast to have sales of $1.2 billion in 2017, according to Wall Street analysts tracked by Thomson Reuters Pharma. 'I GET TO COME HOME AND EAT' Part of the excitement comes from a Phase 1 study last year of nivolumab, which showed lasting response rates among 20 percent to 30 percent of a group of patients with multiple cancers, including lung cancer, a leading cause of cancer death that so far has shown limited response to immune system therapies. The trials are still in the early stages. Researchers are working to understand why most patients do not respond and are exploring combining immunotherapies with other treatments. Aside from the nuisance of frequent blood draws, Tartaglia has had few complaints. “The best part is, I get to come home and eat. I'm all set. Other people are throwing up,” he said of patients at Yale Cancer Center in New Haven who are still getting conventional chemotherapy. Normally, experimental cancer drugs are only used in patients who fail other treatments, said Dr Scott Gettinger, Tartaglia's doctor and an associate professor of medical oncology at the center. “Now we are starting to use immunotherapy drugs as first-line treatments … I know what first-line chemotherapy can do for lung cancer, and it's not great.” Patients with non-small-cell lung cancer, the most common form of lung cancer, who are treated with the current standard of care - chemo and Roche's Avastin - have a median survival of about a year, Gettinger said, noting that some of his patients have been on nivolumab for more than three years. “We haven't really realized the potential of this therapy,” he said. “As we learn how to use this drug, we are going to see higher response rates.” Another of Gettinger's patients, 68-year-old Bruce Leonard, tried chemotherapy, but his lung cancer returned after two years, prompting a decision to enter the nivolumab study. “I felt at the time that by just doing chemo again, at best I would see the same result,” the retired commodity buyer said. “About two months after I started (the trial), there was a 30 percent improvement … and it has gotten progressively better, to the point that with my last scan they found absolutely nothing.” Many patients do not respond to the treatments, but for those who do, the responses have been extraordinary; some patients have lived for years. Yervoy, Bristol-Myers' breakthrough melanoma treatment, only benefits about 10 to 15 percent of patients. Newer agents, such as nivolumab, have shown response rates ranging from 20 percent to 40 percent. A small study released earlier this month looking at a combination of the two drugs showed 53 percent of patients had their tumors shrink by at least half after 12 weeks. In 18 percent of patients on the dual therapy, tumors were no longer detectable. Bristol-Myers has three late-stage clinical trials of nivolumab in melanoma, two late-stage trials in lung cancer and one in kidney cancer. Last November, interim results from an early-phase trial of Merck's lambrolizumab in patients with advanced melanoma showed that it shrank tumors in 51 percent of patients after 12 weeks, compared with a typical response rate of about 5 percent for similar patients given conventional treatment. Merck plans to present an update of this study on June 2 at the ASCO meeting. The company also is studying its anti-PD-1 drug in so-called triple-negative breast cancer, a hard-to-treat form of the disease, as well as head and neck cancer, bladder cancer and lung cancer. Last month, lambrolizumab won designation from the U.S. Food and Drug Administration as a breakthrough therapy, which could speed its approval. “It's clear now that these medicines do have activity across a broader spectrum of tumors, and they seem to be remarkably potent in very challenging clinical oncology settings,” said Dr Gary Gilliland, a senior vice president who heads the oncology franchise at Merck Research Labs. In April, Roche reported results of a small safety study of its anti-PD-L1 drug MPDL3280A that showed anti-tumor activity against a variety of cancers including lung, kidney, colon and gastric cancers. Roche plans to start a Phase III study in lung-cancer patients. The findings are driving enthusiasm for immunotherapies. “It tells us these are poised to be the most important agents in oncology,” said Dr Antoni Ribas of the University of California Los Angeles' Jonsson Comprehensive Cancer Center. Citigroup research analyst Andrew Baum expects immunotherapies to form the backbone of treatments for up to 60 percent of cancers over the next decade, up from less than 3 percent today, transforming the treatment of cancer from a desperate struggle with death into a chronic disease, in which treatments keep patients alive for years. Baum estimates that would generate annual sales of $35 billion. “The current explosion in all ongoing approaches ... to utilize the immune system to seek and destroy cancer cells marks a watershed, analogous to the impact of HIV drugs transforming life expectancy in (patients infected with) HIV,” Baum said in a recent note to investors. YEARS, NOT MONTHS Doctors have been trying for decades to get the immune system to fight cancer with limited, sporadic success. But the disease has developed wily defenses that camouflage tumor cells. “The tide really turned in 2010 with the first presentation of pivotal data about ipilimumab,” said Dr Jedd Wolchok of Memorial Sloan Kettering Cancer Center of the drug now sold as Yervoy. In 2011 ipilimumab became the first immunotherapy drug to help extend the lives of patients with advanced melanoma. “We're very pleased that Yervoy prolongs survival in one out of five individuals, but there is still room for growth,” said Michael Giordano, senior vice president of global development for oncology and immunology at Bristol-Myers. “Our goal here is to have very long-term durable responses. We're not just trying to increase the patient's disease-free survival for a few months,” said Nils Lonberg, senior vice president of discovery biologics at Bristol-Myers. Lonberg envisions a day when immunotherapy will be as important a tool for oncologists as surgery, radiation and chemotherapy. Wolchok says the promise for immunotherapies is treatment responses that last. “The immune system is a dynamic organ. It remembers things,” he said.source : http://www.foxnews.com/health/2013/05/31/immunotherapy-is-not-just-for-melanoma-anymore/