Cancer progress for Merrimack

NAPOLI-1 had three arms: MM-398 combined with 5-fluorouracil (5-FU) and leucovorin, MM-398 as a monotherapy and 5-FU and leucovorin as the control. The combination therapy of MM-398, 5-FU and leucovorin produced an overall survival of 6.1 months, versus the 4.2 months seen in the control arm, and also saw a statistically significant advantage in progression-free survival (PFS), with a median of 3.1 months versus 1.5 months in the control arm. Overall response rate was also improved, showing 16 percent in the combination arm and 1 percent in the control arm. In addition, safety and efficacy for patients receiving MM-398 were consistent with previously reported top-line data and results from earlier clinical studies.

The results for MM-398 as a monotherapy were less encouraging, with the monotherapy posting a 4.9-month median overall survival, just over the 4.2 months seen in the control, and a median PFS of 2.7 months versus the 1.6 months of the control arm. The overall response rate in the monotherapy arm was 6 percent, compared to 1 percent in the control.

“These positive results further strengthen our belief in the MM-398 combination and design of NAPOLI-1. Entering into a difficult disease with a history of clinical trial failures, the MM-398 combination has extended overall survival while striking an important balance between efficacy and toxicity in a setting where there is no current standard of care,” Dr. Eliel Bayever, a vice president at Merrimack and medical director for MM-398, said in a news release. “This Phase 3 success bolsters our confidence in our systems approach and continued commitment to engineering innovative therapies for difficult-to-treat cancers.”

The trial’s outcome is especially good news, says Peter Laivins, head of development at Merrimack, given how few options there are on the market for pancreatic cancer. In light of the results, he adds, they have seen strong interest from a number of investigators to try and bring the regimen into frontline settings.

“There have only been three or four drugs approved in pancreatic cancer over the last 30 or 40 years, and so many failures, too numerous to count, of promising new drugs in this area,” says Laivins. “The full expectation is that if you run a trial in advanced pancreatic cancer, you’re very likely to fail. So we’re very encouraged that our study was successful.”

“As opposed to other types of cancer where survival is measured in months and years in the metastatic setting, in pancreatic cancer, it’s probably the worst of the worst cancers; about 75 percent or more patients will die within a year of treatment,” he continues. “In this case, these patients are measuring their life expectancy with treatment in terms of weeks and months, so to have a drug that provides 45 percent longer overall survival … is really welcome news, and I think the pancreatic cancer community was very excited to see that there was another option now for their patients.”

According to the American Cancer Society, the one-year and five-year mortality rates for pancreatic cancer patients are 73 percent and 94 percent, respectively. Some 46,000 people are diagnosed with this cancer each year, and approximately 40,000 die of it annually; it is the fourth most common cause of cancer death.

Merrimack plans to submit a New Drug Application for the MM-398 combination therapy this year. The compound received orphan drug designation from both the U.S. Food and Drug Administration and the European Medicines Agency in 2011.

The compound is also being investigated in a Phase 2 study in metastatic colorectal cancer patients and Phase 1 studies in Ewing’s sarcoma and glioma. A Phase 1 trial is also being conducted to assess a potential companion diagnostic for MM-398 in a number of cancer types to identify patients most likely to respond to treatment with MM-398.