Celldex Therapeutics' Varlilumab Continues to Demonstrate Very Favorable Profile

“Celldex Therapeutics, Inc. (Nasdaq:CLDX) today reported data from its ongoing Phase 1 study of the fully human monoclonal antibody varlilumab (CDX-1127) in cancer. Varlilumab is an immunotherapy designed to enhance the body’s natural immune response by directly activating T cells that can specifically recognize and kill cancer cells. Preclinical data support the broad study of varlilumab in combination with a number of other anti-cancer agents including but not limited to checkpoint inhibitors, chemotherapies, targeted therapies and vaccines. Varlilumab will enter at least four combination studies in the second half of 2014.”

Editor’s note: As mentioned above, varlilumab is an immunotherapy that works by boosting a patient’s own immune system to fight cancer. In a clinical trial testing the drug in volunteer patients, it shown promise for treating several different types of cancer, including metastatic melanoma.


Clinical Trials Slated for Treatment That Shrinks All Tumors Tested

Last year, a PNAS study showed that the surfaces of many tumor cells have a protein called CD47, which protects them from the immune system. But when these tumors are treated with a drug that inhibits CD47, they get attacked by immune system cells. The researchers transplanted seven kinds of human tumors into mice and treated them with the CD47-targeting drug. All of the tumors—bladder, brain, breast, colon, liver, ovary, and prostate—shrank or disappeared, which kept them from spreading. Now, the research will progress to clinical trials, thanks to a $20 million grant from the California Institute for Regenerative Medicine. CD47 was originally found on leukemia and lymphoma cells; the initial trial will target the stem cells that perpetuate acute myeloid leukemia. This cancer of the blood and bone marrow is fatal within months if untreated, and the 5-year survival rate is only 30% to 40%, even with aggressive treatments including chemotherapy and bone marrow transplants.


Clinical Trials Slated for Treatment That Shrinks All Tumors Tested

Last year, a PNAS study showed that the surfaces of many tumor cells have a protein called CD47, which protects them from the immune system. But when these tumors are treated with a drug that inhibits CD47, they get attacked by immune system cells. The researchers transplanted seven kinds of human tumors into mice and treated them with the CD47-targeting drug. All of the tumors—bladder, brain, breast, colon, liver, ovary, and prostate—shrank or disappeared, which kept them from spreading. Now, the research will progress to clinical trials, thanks to a $20 million grant from the California Institute for Regenerative Medicine. CD47 was originally found on leukemia and lymphoma cells; the initial trial will target the stem cells that perpetuate acute myeloid leukemia. This cancer of the blood and bone marrow is fatal within months if untreated, and the 5-year survival rate is only 30% to 40%, even with aggressive treatments including chemotherapy and bone marrow transplants.


Clinical Trials Slated for Treatment That Shrinks All Tumors Tested

Last year, a PNAS study showed that the surfaces of many tumor cells have a protein called CD47, which protects them from the immune system. But when these tumors are treated with a drug that inhibits CD47, they get attacked by immune system cells. The researchers transplanted seven kinds of human tumors into mice and treated them with the CD47-targeting drug. All of the tumors—bladder, brain, breast, colon, liver, ovary, and prostate—shrank or disappeared, which kept them from spreading. Now, the research will progress to clinical trials, thanks to a $20 million grant from the California Institute for Regenerative Medicine. CD47 was originally found on leukemia and lymphoma cells; the initial trial will target the stem cells that perpetuate acute myeloid leukemia. This cancer of the blood and bone marrow is fatal within months if untreated, and the 5-year survival rate is only 30% to 40%, even with aggressive treatments including chemotherapy and bone marrow transplants.


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.

Primary source: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970090-6/abstract


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.

Primary source: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970269-3/abstract


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.

Primary source: http://www.nejm.org/doi/full/10.1056/NEJMoa1203421


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.