after taking nothing but the Ambit drug. The responses lasted a median time of 3.5 months. Side effects included nausea, vomiting, diarrhea, fever, headache, and fatigue, most of which were mild to moderate in severity, researchers said.
“The patients who enrolled in this trial had a median of three separate rounds of prior treatment, representing a heavily pre-treated population. Yet, we are seeing responses for nearly one out of three patients, which is very encouraging,” said Jorge Cortes, the deputy chair of the Department of Leukemia at MD Anderson Cancer Center in Houston and principal investigator for the study, in an Ambit statement. “The fact that we are seeing these responses for significant durations of time, and in a monotherapy trial where optimal dosing has not yet been determined is really exciting; we were not expecting to see this kind of data in what was originally designed to be a safety study.”
The results were so promising that the company met with the FDA afterwards to form a plan to run a more rigorous clinical trial that could pave the way for Ambit to bring the drug to the market, Salka said.
The company is now gearing up for that trial, which could give the company its first marketed drug in the U.S. The trial will enroll 180 patients who will get AC220, and the study will not randomly assign any patients to a comparison group, because there is no established standard of care for patients with relapsed acute myeloid leukemia. The trial will restrict enrollment to patients with a mutation of the FLT3 kinase, the specific target the drug is made to block. About one-third of patients with acute myeloid leukemia, or 4,000 new cases a year, are estimated to have this mutation, which gives them a worse prognosis than other patients, Salka says.
Ambit doesn’t have a mountain of data to build on as it heads into its pivotal trial. The small study disclosed at ASH looked at a variety of doses from 12 milligrams to 450 milligrams. The company picked a dose of 200 milligrams for the pivotal trial based on a subpopulation from the earlier trial, which showed that four of the five patients with active mutations of FLT3 and who got the 200 milligram dose had complete disappearances of their tumors, Salka says.
If Ambit can show anything close to that kind of result in the more rigorous pivotal trial, it should have a winner, Salka says. But to get that answer, it needs more money, he says. That’s likely to come from a partner.
“We have investors with deep pockets, and we’ll likely have a new partner very soon,” Salka says.
Ambit and whoever its partner may be will be up against some formidable competitors pursuing drugs for acute myeloid leukemia. At various stages of development, Novartis has PKC412, Genzyme is working on clofarabine, Cephalon has CEP-701, and Seattle Genetics is testing lintuzumab (SGN-33).
Ambit sees its drug being different in the marketplace because of its specific targeting of FLT3 kinase. If it can confirm this idea in the pivotal study about to get underway, it will be quite a turnaround for a company that’s better known for reinventing itself than for creating a new identity as an emerging cancer drug developer.
“For people who don’t keep a close eye on us, they can’t believe how quickly things have moved for us,” Salka says.
