New Melanoma Immunotherapy Advances in Early Trials

On the strength of a promising phase I clinical trial, evaluations are continuing for an experimental immunotherapy that targets and selectively kills melanoma cells. Called IMCgp100, the drug has two parts that are fused together. One part is an immune system protein that has been engineered to recognize a protein called gp100, which is on the surface of melanoma cells. The other part of the new drug is a protein fragment that boosts the immune response against the tumor. The phase II trial of IMCgp100 is currently recruiting new participants.

New Combination Vaccine for Melanoma Enters Early Clinical Trial

A new clinical trial is underway for an immune system booster that makes an experimental vaccine against melanomas work better. The experimental vaccine is gp100, a protein made by melanoma cells, and the immune system booster is a heat shock protein. The latter got its name because it protects other proteins from heat and other forms of stress, but heat shock proteins also stimulate the immune response. The phase I trial of this combination vaccine will include 12 to 20 people with melanomas that have spread, and is currently recruiting participants.

Revamping the Way Cancer Vaccines Are Made Could Boost Their Efficacy

While not as toxic as other therapy approaches, cancer vaccines have also not been very effective. Despite many attempts by researchers, the only therapeutic cancer vaccine that has been approved by the Food and Drug Administration (FDA) is sipuleucel-T (Provenge), which is approved specifically for men with metastatic prostate cancer. Continue reading…

Ipilimumab Could Treat Small Melanomas in the Brain

A study in The Lancet shows that the drug ipilimumab could treat melanomas that have spread to the brain, particularly in people who do yet not have neurological symptoms. Of 51 such patients treated with ipilimumab, 12 had tumors in the brain that shrank or did not get worse and 14 had tumors outside the brain that shrank or did not get worse. Ipilimumab (Yervoy) is an immune system booster that the FDA has approved for treating advanced melanomas.

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Drug Targets Two Common Melanoma Mutations

An experimental drug could help control some melanomas that have BRAF or NRAS mutations, according to a report at an American Society of Clinical Oncology meeting. Tumors shrank or did not get worse in 8 out of 35 patients with the most common BRAF mutation (V600E), and in 6 out of 28 patients with NRAS mutations. This is the first targeted treatment for melanomas that have NRAS mutations. BRAF and NRAS mutations can activate a protein called MEK that is involved in cell division. The experimental drug, which is called MEK162, is a MEK inhibitor. The side effects of MEK162, which included diarrhea, rashes and swelling, were manageable.

Dabrafenib May Shrink Melanomas in the Brain

An early stage clinical trial suggests that dabrafenib, a BRAF inhibitor, could treat melanomas that have spread to the brain. The study, reported in The Lancet, included 10 people with brain metastases of melanomas that had BRAF mutations. Tumors shrank in 9 patients and were not evident in 4 patients. This is a surprise because the drug had not been expected to cross the blood-brain barrier effectively. Indeed, melanoma patients with brain metastases have been routinely excluded from previous trials of vemurafenib (Zelboraf) and other BRAF inhibitors.

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Trametinib Outperforms Chemotherapy for Melanomas with BRAF Mutations

A New England Journal of Medicine study reports a promising new approach to treating melanomas with BRAF mutations, which often respond to BRAF inhibitors for just a short time. Melanoma patients treated with trametinib were stable (ie, did not get worse) for three times longer than those treated with dacarbazine, a conventional chemotherapy drug (4.8 vs. 1.5 months, respectively). Trametinib inhibits MEK, a protein that is activated by BRAF and is involved in cell division. The drug’s most common side effects were rash, diarrhea, and swelling in the legs, which could be controlled by periodically adjusting the dose.

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New Melanoma Mutation Frequent Enough for Routine Screening

Researchers identified a new mutation (BRAF L597) in a melanoma patient and then tested for it in 49 other melanomas that had no known cancer-linked mutations, which account for about half of all melanomas. They found that BRAF L597 occurred in 4% of the other melanomas tested. The study, which appeared in Cancer Discovery, also showed that tumors with this mutation respond to a MEK inhibitor called TAK-733. The existence of a targeted treatment, coupled with the new mutation’s relatively high incidence, lead the researchers to suggest routinely screening melanomas for BRAF L597.

UK Health Institute Approves Vemurafenib and Ipilimumab for Melanomas

The National Institute for Health and Clinical Excellence (NICE) recommends giving people in England and Wales access to vemurafenib and ipilimumab via the National Health Service (NHS). The FDA has already approved these drugs for treating metastatic melanoma in the U.S. Initially, the cost of these treatments was a stumbling block in the UK and the watchdog institute’s recommendation comes with the caveat that manufacturers must provide a discount to the NHS.