Relatlimab/Nivolumab Combo Active in Melanoma After PD-1/PD-L1 Therapy


“Half of patients with melanoma who progressed on anti–PD-1/PD-L1 therapy benefited from the combination of nivolumab (Opdivo) and the LAG-3 inhibitor relatlimab (BMS-986016), data from a dose-expansion study showed.

“The combination led to objective responses in 7 of 61 evaluable patients, increasing to 18% in a subgroup of patients LAG-3–positive tumors. Half of all patients treated and two-thirds of those patients with LAG-3–positive tumors derived clinical benefit, as reported at the 2017 ESMO Congress.”

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Melanoma News at ASCO 2017: Combination Treatments

There are many hopes that combining immune checkpoint inhibitor drugs, or combining them with drugs of other types (immunotherapy, targeted therapy, or chemotherapy) is the future of treatment for many kinds of cancer. Literally hundreds of clinical trials are actively exploring these combinations, and melanoma is the cancer for which trials of this type abound. Last month, the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago featured just a few presentations in this area, apparently because it is too early to report results from the many ongoing trials with drug combinations. Continue reading…

Immune Checkpoint Inhibitors in Melanoma: New Directions

The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…

Molecular Pathways: Co-Expression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy

“The expression of immune checkpoint molecules on T cells represents an important mechanism that the immune system uses to regulate responses to self-proteins. Checkpoint molecules include CTLA-4 (Cytotoxic T Lymphocyte Antigen-4), PD-1 (Programmed Death-1), LAG-3 (Lymphocyte Activation Gene-3), TIM-3 (T cell Immunoglobulin and Mucin protein-3) and several others. Previous studies have identified individual roles for each of these molecules, but more recent data show that co-expression of checkpoint molecules occurs frequently on cancer-specific T cells, as well as on pathogen-specific T cells in chronic infections. While the signaling pathways associated with each checkpoint molecule have not been fully elucidated, blocking multiple checkpoints with specific monoclonal antibodies results in improved outcomes in several chronic viral infections as well as in a wide array of pre-clinical models of cancer. Recent clinical data suggest similar effects in patients with metastatic melanoma. These findings support the concept that individual immune checkpoint molecules may function through non-overlapping molecular mechanisms. Here we review current data regarding immune checkpoint molecule signaling and co-expression, both in cancer and infectious disease, as well as the results of preclinical and clinical manipulations of checkpoint proteins.”