AstraZeneca-Novartis Three-Drug Melanoma Treatment Found Safe

A first-of-its-kind combination of three drugs to treat a deadly form of skin cancer can be taken safely, passing the first hurdle to regulatory approval for a potentially long-lasting treatment.

The treatment was tested in an early-stage trial that was a collaboration between AstraZeneca Plc and Novartis AG. Researchers combined two drugs, dabrafenib and trametinib -- a so-called doublet therapy that has been proven effective in targeting melanomas with mutations in the BRAF gene -- with an immune system-based treatment that may prevent the disease from relapsing.

Dabrafenib, sold as Tafinlar, and trametinib, sold as Mekinist, were developed by GlaxoSmithKline Plc and acquired by Novartis in March. The immune therapy drug, MEDI4736, is being developed by AstraZeneca.

Melanoma is a rare but deadly form of skin cancer for which a number of drugs have been approved in recent years. Among them are BRAF inhibitors like dabrafenib, which target mutations found in about half of all melanoma patients, as well as immune therapies like Bristol-Myers Squibb Co.’s Yervoy, which unleash the body’s own immune system. Because the immune system can be trained, those therapies may be more durable than other forms of treatment.

Trametinib inhibits MEK, a protein activated by BRAF. While combining the two inhibitors has proven effective in melanoma, combining BRAF inhibitors with immune therapies has so far been unsuccessful, said Mohammed Dar, vice president for clinical development in oncology at MedImmune, AstraZeneca’s biotech unit. AstraZeneca is hoping its MEDI4736 will be better tolerated by patients than other immune therapies, he said.

Manageable Side Effects

“Our rationale was that the field was already moving toward the doublet therapy,” Dar said in an interview before the data was released. “We wanted to see if we could add immune therapy on top of what was becoming the standard of care.”

The trial, a collaboration between AstraZeneca and Novartis, treated 50 patients with the drugs in various combinations. While patients reported fatigue, fever and vomiting, the study concluded the side effects were manageable.

A summary of the results was released Wednesday by the American Society of Clinical Oncology, and will be presented at the group’s meeting that begins May 29.

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