Earlier this year, the US Food and Drug Administration (FDA) granted its first ‘breakthrough therapy designations’ to a pair of cystic fibrosis drugs (see Nat. Med. 19, 116–117, 2013). But since then, it’s been all about the cancer agents.

The New Jersey drug giant Merck announced this morning that its investigational cancer drug lambrolizumab (MK-3475) had received the breakthrough blessing in recognition of the dramatic clinical benefits observed in an open-label, phase 1 trial involving people with advanced melanoma. The FDA’s new development path is specifically designed for experimental agents that produce large and unprecedented treatment effects in early clinical trials.

According to preliminary data presented at an international melanoma meeting last year, 43 of 85 patients with inoperable and metastatic melanoma who received lambrolizumab showed an objective anti-tumor response after 12 weeks, including eight who experienced a complete response. The average duration of response was 7.6 months, and most of the reported side events were minor, although seven people experienced potentially dangerous immune-related complications.

“It’s never a good time to be a patient. But at this point, if you are, it’s the dawning of a new day where we have the return of hope of having a significant therapy,” says trial investigator Omid Hamid, director of the Melanoma Center at the Angeles Clinic and Research Institute in Los Angeles.

“One of the best things about getting this breakthrough designation is that it drives patients to clinical trials, and it drives patients to the understanding that there is continued work being done,” he adds.

Nature

Like Yervoy (ipilimumab), an FDA-approved melanoma therapy that promotes T cell function by blocking a surface protein called cytotoxic T lymphocyte antigen 4 (CTLA-4), lambrolizumab is an immunotherapy drug. It works by inhibiting another surface protein called programmed death-1 (PD-1). PD-1 is an inhibitory signaling receptor expressed on activated T cells. By targeting PD-1, lambrolizumab stimulates the immune system, enhancing the ability of T cells to kill tumor cells (see Nat. Med. 18, 993, 2012).

Bristol-Myers Squibb, Genentech, Amplimmune and CureTech all similarly have drugs directed at either PD-1 or its ligand. But, according to Hamid, lambrolizumab is the only drug to have been shown publicly to work in people for whom Yervoy has failed. In the trial data presented last year, 11 of 27 participants who had previously tried Yervoy showed an objective anti-tumor response to the new experimental Merck antibody.

Additional phase 1 data will be presented in June at the American Society of Clinical Oncology’s annual meeting in Chicago. Merck is currently recruiting participants for a 510-person, phase 2 follow-up.

Wendy Selig, president and chief executive of the Melanoma Research Alliance, an advocacy organization based in Washington, DC, welcomes the new designation for lambrolizumab. “We view it as a really important step in the process of creating this ‘all hands on deck’ mentality, where you have a serious unmet medical need and where there are big gaps in terms of what’s available,” she says.

Lambrolizumab is the fourth experimental cancer drug to be labeled a breakthrough. The others are: Pfizer’s palbociclib (PD-0332991) for metastatic breast cancer; Novartis’s LDK378 for ALK-positive lung cancer; and Johnson & Johnson’s ibrutinib (PCI-32765) for various types of leukemia and lymphoma.

“It’s great to see that the FDA has embraced this,” says Jeff Allen, executive director of Friends of Cancer Research, a Washington, DC–based think tank and advocacy organization that first proposed the breakthrough designation. “I think what’s most promising is that there are drugs that are having this magnitude of effects in disease settings where there are so few options.”