“A majority of patients with advanced melanoma who had and had not received previous ipilimumab demonstrated durable responses with the PD-1 targeted antibody MK-3475, according to study results presented at the ASCO Annual Meeting.
“ ‘This is the largest phase 1 clinical trial ever conducted in this disease, and together with a lung cancer cohort, this is the largest phase 1 trial ever done in oncology,’ study investigator Antoni Ribas, MD, PhD, professor of medicine at the David Geffen School of Medicine at the University of California in Los Angeles, said during a press conference. ‘These are early data, but they tell us we are on to something really important.’ ”
Editor’s note: The cancer drug MK-3475 is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. This story describes a clinical trial that tested MK-3475 on volunteer patients with advanced melanoma, and found good results for a majority of the patients. Some of the patients had previously been treated with the drug ipilimumab (Yervoy) and some had not; both kinds of patients benefited from MK-3475 in the trial.
“Among patients with non-small cell lung cancer (NSCLC) treated with the investigational immune checkpoint inhibitor MK-3475, those whose tumors had high levels of the protein PD-L1 had significantly better outcomes, according to results of a phase I clinical trial presented here at the AACR Annual Meeting 2014, April 5-9.
“Preliminary data from the trial, which were reported earlier this year, showed that MK-3475 treatment was well tolerated and led to durable, objective responses in previously treated patients with NSCLC, particularly those with tumors found to have high levels of PD-L1 prior to treatment.
“The latest results extend these data, showing that at six months after starting treatment, 41 percent of patients whose tumors had high levels of PD-L1 had no disease progression, compared with 17 percent of those whose tumors had low levels of PD-L1. Similarly, 72 percent of patients whose tumors had high levels of PD-L1 were alive at this time, compared with 53 percent of those whose tumors had low levels of PD-L1.”
Editor’s note: MK-3475 is an immunotherapy drug, which means it boosts a patient’s own immune system to fight cancer. This study found that it was more effective in patients whose tumors had high levels of the protein PD-L1, as detected by molecular testing. To learn more about immunotherapy treatments for lung cancer, visit this blog post.
“Among melanoma patients treated with the PD-1 inhibitor MK-3475, those whose tumors had the protein PD-L1 had better immune responses and higher survival rates, according to results presented here at the AACR Annual Meeting 2014, April 5-9.
“When the protein PD-L1, which is present on some melanoma tumors, binds to PD-1, a protein present on T cells, “brakes” are applied on these T cells, preventing them from attacking the cancer cells. The immunotherapy MK-3475 blocks PD-1, releasing the brakes on T cells and enabling them to attack the cancer cells.”
Three new immunotherapy drugs for non-small cell lung cancer (NSCLC) – nivolumab, lambrolizumab (MK-3475), and MPDL-3280A – have produced encouraging early results. All three interfere with PD-1 and PD-L1, molecules that interact to shield tumors from being attacked by the body’s immune system. In phase I trials, more than 20% of participants experienced tumor shrinkage in response to each of the three drugs. For these patients, effects tended to be rapid and long-lasting. Most continue to respond favorably to treatment at this time, having been in the trials for up to 7 months (MPDL-3280A), an average of 9 months (lambrolizumab), or an average of 1.5 years and ranging up to 2.5 years (nivolumab). Overall toxicity was acceptable, though some cases of severe side effects were seen, including two deaths with nivolumab.
Erin Youngerberg was diagnosed with melanoma in October, 2010, at age 32 years. Well-traveled and an avid photographer, she grew up in Minnesota, went to college and worked in Milwaukee, then made her way east, living in Ohio and North Carolina before ending up in Jersey City, just outside of New York City. After her diagnosis, she started a blog to keep folks back home updated. Called ‘Melanoma and the City,’ it tells the whole story: from appointments at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City to various city adventures; from treatment side effects to recipes for quinoa and tacos. Erin has also found herself dedicated to spreading the word about melanoma awareness. We asked her to take us through her melanoma story.Continue reading…
In the last few years, patients with the grim diagnosis of metastatic melanoma have gained reasons to feel more hopeful about their chances of beating the disease. Melanoma has become a poster child for new cancer treatment options, with several targeted and immune therapies approved by the U.S. Food and Drug Administration (FDA) and many more in clinical development. Continue reading…
Sullivan RJ, LoRusso PM, Flaherty KT. Clinical Cancer Research. Oct 1, 2013.
“In three years, four drugs have gained regulatory approval for the treatment of metastatic and unresectable melanoma, with at least seven other drugs having recently completed, currently in, or soon to be in phase III clinical testing. This amazing achievement has been made following a remarkable increase of knowledge in molecular biology and immunology that led to the identification of high-valued therapeutic targets and the clinical development of agents that effectively engage and inhibit these targets. The discovery of either effective molecularly targeted therapies or immunotherapies would have led to dramatic improvements to the standard-of-care treatment of melanoma. However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP–ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of molecularly targeted therapies, immunotherapies, and molecular targeted therapies with immunotherapies. This overview presents the historical context to this therapeutic revolution, reviews the benefits and limitations of current therapies, and provides a look ahead at where the field is headed.”
Results of an ongoing phase I clinical trial reinforce the promise of an experimental immunotherapy drug against melanoma. The drug, lambrolizumab, blocks a protein called PD-1, which lets cancer cells evade the immune system. In the new study, researchers gave lambrolizumab to 135 people with melanomas that had spread. Tumors shrank in more than half of those who got the highest dose of lambrolizumab (10 mg per kilogram every 2 weeks), and disappeared completely in 12 people. Moreover, tumors still had not grown again more than a year later. Side-effects were generally mild. This trial is currently accepting new participants.
Following in the footsteps of positive results for the drug nivolumab, another anti-PD1 antibody, lambrolizumab (formerly MK-3475), is also showing promising activity in melanoma. At the annual meeting of the American Society of Clinical Oncology, Antoni Ribas, MD, PhD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, presented data from a large, 1,000-plus patient phase I trial that also included other cancer types. Continue reading…