Amgen Receives CHMP Positive Opinion For IMLYGIC™ (Talimogene Laherparepvec)

“Amgen AMGN, +1.94% today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion recommending that IMLYGIC™ (talimogene laherparepvec) be granted approval for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease. If approved by the European Commission, IMLYGIC would be the first in a class of novel agents known as oncolytic immunotherapies.

“IMLYGIC, administered via intralesional injection, is designed to cause the death of tumor cells and to initiate an anti-tumor immune response.”


A Subset of Patients with Metastatic Melanoma Achieves Clinical Benefit from Combination of Immunotherapy and Radiation Therapy

“Immunotherapy combined with palliative radiation therapy (RT) for a subset of patients with metastatic melanoma reduces the growth and spread of the cancer, according to research presented today at the American Society for Radiation Oncology’s (ASTRO’s) 57th Annual Meeting.

“Although melanoma is not the most common type of skin cancer, it is the most serious type. Stage IV melanoma indicates that the cancer has metastasized and spread through lymph nodes to distant sites in the body and/or to the body’s organs. The liver, lungs, bones and brain are areas most frequently affected by these metastatic lesions. Immunotherapy—the use of medicines to stimulate a patient’s own immune system to recognize and destroy cancer cells more effectively—can be combined with other cancer therapies to aid in the treatment of stage IV melanoma. Ipilimumab is an immunotherapy approved for use in melanoma patients.

“This phase II clinical trial is one of the first prospective clinical trials to report results from the treatment of metastatic melanoma with the combination of RT and systemic immunotherapy. In this study, 20 patients with stage IV melanoma were treated with palliative RT and intravenous ipilimumab (3mg/kg) every three weeks, for a total of four treatment cycles. RT was initiated to one or two sites of metastatic melanoma within five days of the initial immunotherapy treatment. All patients had at least one nonirradiated (untreated) site of metastasis that could be used for assessment of response to therapy.”


Surgery on Melanoma That Has Spread into Abdomen More than Doubles Patient Survival Time

“Patients with metastatic melanoma who undergo surgery to remove lesions that have spread into the abdomen live more than twice as long as those treated with drug therapy alone, according to novel new research by a North Shore-LIJ Health System cancer surgeon.

“The study, by North Shore-LIJ surgical oncologist Gary B. Deutsch, M.D., M.P.H., will be presented on Oct. 8 at the 2015 Clinical Congress of the American College of Surgeons in Chicago. Dr. Deutsch’s research is the first comprehensive look at the survival benefits of surgical resection for melanoma metastases in the abdomen since the advent of groundbreaking immunotherapies in recent years that stimulate patients’ immune systems to destroy cancer cells, improving once-dismal survival rates.

“Dr. Deutsch’s study could immediately impact how oncologists across the United States approach metastatic melanoma cases in which the cancer has spread to abdominal organs, he said.”


Nivolumab/Ipilimumab Combination FDA Approved for BRAF Wild-Type Melanoma

“The combination of nivolumab and ipilimumab has received accelerated FDA approval as a treatment for patients with BRAF V600 wild-type (WT) unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study.

” ‘Historically, metastatic melanoma has been a difficult disease to treat. Now, a new treatment option based on the combination of two valued immuno-oncology agents demonstrates significant efficacy versus ipilimumab in metastatic melanoma,’ said Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, in a statement. ‘Today’s approval represents a step forward for the melanoma community, providing hope for patients with metastatic melanoma.’ ”


Combining Two Targeted Therapies Results in Melanoma Patients Living Significantly Longer

“Latest results from a trial of a combination of two targeted therapies (dabrafenib and trametinib) to treat advanced melanoma have shown that patients are living significantly longer on the combined therapy than patients treated with another drug, vemurafenib, when used alone.

“Professor Caroline Robert, of the Institut Gustave Roussy, Paris, France, will tell the 2015 European Cancer Congress today (Monday) that not only is the median overall survival time longer for patients receiving the combination treatment, but also that 51% of patients receiving the combination treatment are alive after two years, compared to 38% of patients receiving vemurafenib alone.

“Analysis of data up to 13 March 2015 showed that the median overall survival time among patients with metastatic melanoma harbouring V600 mutations in the BRAF gene who received the combination treatment was 25.6 months. Among patients receiving vemurafenib alone, it was 18 months. On the basis of this finding, the European Commission approved the combination of dabrafenib and trametinib for use in Europe for these patients on 1 September 2015.”


Melanoma Brain Metastases: Q&A With Keith Black, MD

“Malignant melanoma is one of the most common primary tumors to spread to the brain. In close to 50% of patients who have metastatic melanoma, the disease can be found in their brain.

“For example, in former President Carter’s case, the cancer was first found in his liver and later removed. During his press briefing last month, he announced that the melanoma had metastasized to his brain, and he was beginning treatment with pembrolizumab immediately.

“In order to learn more about melanoma metastases to the brain, Targeted Oncology interviewed Keith Black, MD, chairman and professor, Department of Neurosurgery, Cedars-Sinai Medical Center, director, Maxine Dunitz Neurosurgical Institute, director, Johnnie L. Cochran, Jr, Brain Tumor Center, and Ruth and Lawrence Harvey Chair in Neuroscience.”


Frequency of Certain Immune Cells in Blood May Predict Metastatic Melanoma Response to Pembrolizumab

“Among patients with metastatic melanoma treated with the immunotherapy drug pembrolizumab (Keytruda), those whose cancer responded to the treatment had a higher frequency of immune cells called T cells that were positive for the proteins CD8, PD-1, and Bim (CD8+PD-1+Bim+ T cells) in blood samples taken immediately before starting pembrolizumab than those who had disease progression, according to data presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, held Sept. 16–19.

“Pembrolizumab, which targets the protein PD-1, was approved by the U.S. Food and Drug Administration for treating metastatic melanoma in September 2014. Some patients with metastatic melanoma have remarkable responses to pembrolizumab, whereas others do not respond at all, according to Roxana S. Dronca, MD, a medical oncology consultant and assistant professor of oncology at the Mayo Clinic in Rochester, Minnesota.”


Video: Efficacy of PD-1/PD-L1 Inhibitors in Melanoma

“Jason J. Luke, MD, FACP, assistant professor of medicine, The University of Chicago, discusses the efficacy of PD-1/PD-L1 inhibitors in melanoma. The combination of these inhibitors, nivolumab and ipilimumab, was used to treat patients with previously untreated, unresectable or metastatic melanoma, in the Checkmate 069 study.

“Luke says PD-L1 is very complex and difficult when developing immunohistochemical assays. Since several pharmaceutical companies conduct different assays that test various things, a particular patient may be positive in one case, but not in another. For this reason, patients become very confused.

“Luke also mentions that there is no validated method across the board, so it is difficult to determine the next steps going forward.”


What Determines Whether a Melanoma Patient Will Respond to Checkpoint Blockade Drugs?


Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…