“A study by J. William Harbour, M.D., Associate Director for Basic Research and leader of the Eye Cancer Site Disease Group at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, and colleagues, published today in Clinical Cancer Research, details the discovery of a biomarker that puts patients at a higher risk for metastasis of uveal melanoma.
“Among uveal melanomas categorized as class 1, those with high levels of the biomarker PRAME mRNA were more likely to metastasize than those with low levels of PRAME mRNA, indicating that patients with this biomarker be monitored more closely for metastatic disease.
“The estimated five-year rate of metastasis was 0 percent for PRAME mRNA–low class 1 uveal melanomas and 38 percent for PRAME mRNA–high class 1 uveal melanomas. This research builds upon Harbour’s identification of class 1 and 2 uveal melanomas in 2004.”
“The FDA granted orphan drug designation to IMCgp100 for the treatment of uveal melanoma.
“IMCgp100 (Immunocore) is part of a class of bispecific biologic reagents known as ImmTACs, or immune-mobilizing monoclonal T-cell receptors against cancer.
“The agents combine a T-cell receptor-based targeting system with an anti-CD3 effector function designed to activate a specific and potent T-cell response to recognize and destroy cancer cells, according to Immunocore.”
“As the field of liquid biopsies for tracking disease progression and therapeutic response heats up, many doctors are looking for ways to apply this approach to their patients. Currently, assays for circulating tumor cells (CTCs) – one type of liquid biopsy – have been approved for diagnostic purposes in metastatic breast, colorectal, or prostate cancer. In these diseases, the presence of CTCs in the peripheral blood is associated with decreased progression-free survival and decreased overall survival. The major challenge for this technology is that CTCs are not always found in the blood of patients with aggressive disease who would be expected to have high numbers. Now, researchers at Thomas Jefferson University investigating uveal melanoma, a type of melanoma that originates in the eye, have shown that the low numbers could simply be explained by where the blood is drawn – whether from a vein or an artery.”
“AstraZeneca’s much anticipated cancer drug pipeline suffered a modest blow on Wednesday when the experimental drug selumetinib failed to meet its goal in a late-stage trial for a rare cancer of the eye.
“The drugmaker said the disappointing result in uveal melanoma would not affect other studies using the drug. Selumetinib is being investigated primarily as a treatment for advanced non-small cell lung cancer.
“Selumetinib belongs to a class of cancer drugs known as MEK inhibitors, which includes Novartis’s approved product Mekinist and the experimental compound cobimetinib from Roche and Exelixis.
“Current consensus analyst forecasts for selumetinib, which is designed for use alongside chemotherapy, point to relatively minor sales of $305 million in 2020, according to Thomson Reuters Cortellis.”
“Aura Biosciences, a biotech company developing highly tumor-targeted breakthrough therapies for rare cancers, has been granted Orphan Disease Designation by the FDA for its drug AU-011 for the treatment of Uveal Melanoma. The FDA’s Orphan Drug Designation program provides orphan status to drugs and biologics, which demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions in the US. In addition, the first oral presentation of Aura Biosciences’ pre-clinical research, ‘Evaluating the in vivo efficacy of a first-in-class drug for the treatment of primary uveal melanoma’, was recently delivered by McGill University Health Centre researchers at the ARVO (Association for Research in Vision and Ophthalmology) Annual Meeting.
“ ‘There are currently no approved drug therapies for the treatment of uveal melanoma which is a rare but life threatening disease. We are thrilled to receive this Orphan Drug Designation that, together with the positive preclinical data, is enabling us to move this drug one step closer to the clinic,’ said Elisabet de los Pinos, founder and CEO of Aura Biosciences.”
“A first-in-class immunotherapy called IMCgp100 yielded durable responses in patients with advanced cutaneous melanoma and those with advanced ocular melanoma, according to data from a phase I/IIa clinical trial presented here at the AACR Annual Meeting 2015, April 18-22.
” ‘IMCgp100 is a new type of immunotherapy that has two functional ends,’ said Mark R. Middleton, MD, PhD, professor of experimental cancer medicine at the University of Oxford in the United Kingdom. ‘The targeting end attaches to melanoma cells and the effector end locks on to any neighboring killer T cell [a type of immune cell], resulting in directed destruction of the tumor. One can think of IMCgp100 as a molecular bridge connecting melanoma cells with killer T cells, encouraging the killer T cells to destroy the melanoma cells.
” ‘Last year at the AACR Annual Meeting, we reported the results of the phase I dose-escalation portion of the clinical trial, which showed that IMCgp100 was well tolerated and had efficacy in some patients with advanced melanoma,’ continued Middleton. ‘This year, we are reporting data from 17 patients treated with the maximum tolerated dose of 600 nanograms of IMCgp100 per kilogram or an absolute dose of 50 micrograms of IMCgp100 as part of the phase I and phase IIa portions of the trial.’ “
The gist: The drug ipilimumab showed promise for people with metastatic uveal melanoma in a recent clinical trial that tested it in volunteer patients. Ipilimumab (aka Zelboraf) has shown some success in treating cutaneous melanoma, but had not yet been tested in uveal melanoma. In the trial, ipilimumab was effective for some patients, and almost 25% are still alive two years after treatment; an encouraging outcome for the disease. More uveal melanoma patients will be given ipilimumab in clinical trials as research continues. One of the trials is currently recruiting patients.
“The first trial of the immunomodulator ipilimumab (Yervoy, Bristol-Myers Squibb Company) conducted in patients with malignant uveal melanoma has shown efficacy in some patients.
” ‘After almost 2 years’ follow-up, we can see that almost 25% of patients are still alive, and that is very encouraging in this population of patients with very bad outcome,’ lead investigator Josep Piulats, MD, PhD, from the Institut Catala d’Oncologia and L’Hospitalet del Llobregat in Spain, told Medscape Medical News.
“The results from the study, known as GEM1, were presented in a poster at the recent Society of Melanoma Research (SMR) 2014 International Congress, in Zurich, Switzerland.
“Although the study was small (only 32 patients) and open-label, and although it just missed its primary endpoint of improving overall survival, the researchers say they are encouraged by finding “objective responses in a population of highly metastatic patients.”
Uveal (ocular) melanoma is a difficult-to-treat type of melanoma found in the eye. Remarkably resistant to chemotherapy and prone to metastasis, it is often treated with surgery and/or radiation. Earlier this year, I wrote about new scientific findings that could lead to new targeted treatments for uveal melanoma. These would take advantage of abnormal molecular characteristics of tumor cells. Now, another targeted drug called selumetinib has entered the spotlight. It was recently tested in patients in a clinical trial with promising results. Continue reading…
“In patients with advanced uveal melanoma, treatment with the agent selumetinib, compared with chemotherapy, resulted in an improved cancer progression-free survival time and tumor response rate, but no improvement in overall survival, according to a study. The modest improvement in clinical outcomes was accompanied by a high rate of adverse events.”
Editor’s note: Selumetinib is a targeted drug that may benefit people with ocular melanoma. In a recent clinical trial to test the drug in volunteer patients, selumetinib was compared to standard chemotherapy. More patients treated with selumetinib experienced tumor shrinkage than those treated with chemotherapy, and patients treated with selumetinib experienced a longer lag time (about 4 months, compared to 2 months) before their cancer progressed. However, there was no difference in overall survival between patients treated with selumetinib and patients treated with standard chemotherapy. Unfortunately, almost all of the patients who took selumetinib experienced adverse side effects.