Oncology New Drug May Help Pancreatic Cancer Patients to Live Longer

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Northwestern University Medical School

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Researchers have developed a new drug – elraglusib that may help pancreatic cancer patients to live longer. A phase 2 randomized trial showed that the drug along with chemotherapy reduced the risk of death by 38 %.

Chicago/USA – Pancreatic cancer is one of the deadliest cancers and among the hardest to treat, with most patients surviving less than a year after diagnosis. But a new drug developed at Northwestern University may soon help patients live longer.

In a randomized phase 2 clinical trial, patients who received the experimental drug elraglusib, alongside standard chemotherapy, were twice as likely to be alive after one year of treatment, compared to those receiving chemotherapy alone. The drug also reduced the risk of death by 38 %.

The study is one of only a few successful randomized trials in the last decade to show a survival benefit that would be applicable to a broad population of pancreatic cancer patients, according to the authors. Pancreatic cancer is the third leading cause of cancer-related mortality in the U.S.

The study, which was led by Northwestern Medicine, was published on April 14 in Nature Medicine.

“Pancreatic cancer remains one of the most challenging solid tumors to treat, but these findings provide cautious optimism for patients,” said study lead author Dr. Devalingam Mahalingam, professor of medicine in the division of Hematology and Oncology at Northwestern University Feinberg School of Medicine.

“While these results will need to be confirmed in phase 3 trials, observing survival benefit in such a difficult-to-treat cancer is encouraging. Given the novel mechanism of this drug, these findings raise the possibility that it could have broader application across other tumor types,” added Mahalingam, who also is the associate director of clinical research at Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

How the trial was conducted

The phase 2 trial enrolled 233 patients with metastatic pancreatic cancer across 60 sites in six countries in North America and Europe. Patients were randomly assigned to receive either standard chemotherapy or the same chemotherapy combined with elraglusib.

Those who received elraglusib lived a median of 10.1 months, compared to 7.2 months for those who only received chemotherapy. While that three-month difference may appear modest, it’s partly because the trial included patients whose cancer progressed too quickly to benefit from treatment.

Among patients who benefited from the drug, the impact was pronounced. Twice as many patients who received elraglusib were alive at one year (44 % vs. 22 %) and about 13 % of patients in the drug group were alive at two years, compared to none in the chemotherapy group.

Side effects were generally consistent with chemotherapy but slightly more common in the elraglusib group. The most frequent included low white blood cell counts, fatigue and temporary vision changes, which were reversible. Overall, the safety profile of the drug was considered manageable, the authors said in the study.

‘My husband believed in helping future patients’

Because the trial started more than five years ago in the U.S., most American participants have since died from their cancer. But relatives of two Northwestern Medicine patients who received the drug and lived for roughly two years after starting the trial said participating gave their loved ones a sense of purpose.

Donna Husar, 65, of Palos Heights, Illinois, said her late husband, Matthew, chose to participate shortly after his diagnosis in consultation with a relative who worked in oncology. “If you have any opportunity to go on a trial drug, go for it,” she recalled being told. Matthew Husar remained in the trial for nearly two years, and the family credits the drug with giving them more time together.

For his daughter, Madeline, 29, of Chicago, the clinical trial offered something to hold onto. “When you read about pancreatic cancer online, it’s terrifying,” she said. “But knowing there was research and a trial gave us something positive to focus on instead of stressing about the worst-case scenarios.”

Maria Lepowsky, 75, of Madison, Wisconsin, said the trial experience for her late husband Robert Brightman was similarly meaningful. Brightman participated in the trial for about two years as well.

“My husband believed in helping future patients,” she said, noting that in addition to extending his life, the drug also improved his quality of life.

“Inevitably, there were some serious side effects, but nonetheless, for most of the treatment period, he was able to take the 151 bus to Northwestern Medicine on his own to the clinic. That was really important to him to maintain his autonomy and be as close to normal a Chicago resident as you could be,” Lepowsky said.

How elraglusib works

Elraglusib was developed nearly 15 years ago inside Northwestern University labs. It targets a protein known as GSK-3 beta, which plays a role in tumor growth and suppression of the immune system.

Unlike traditional chemotherapy, which aims to kill cancer cells, elraglusib seems to act on the tumor microenvironment. That’s the mix of cancer cells, immune cells and surrounding tissue that can either support or weaken tumors.

Pancreatic tumors are hard to treat in part because of their microenvironment, which is particularly adept at suppressing immune response. In the study, patients who received elraglusib showed increases in cancer-fighting cells within their tumors, offering early evidence that the drug may help re-engage the immune system.

In addition, certain immune-related markers in the blood at the start of the trial were associated with longer survival among patients who received the drug. While these findings are preliminary, they suggest that elraglusib may be particularly effective in certain patients whose immune systems are already primed to respond.

Mahalingam and his colleagues are exploring a larger confirmatory phase 3 trial as funding and partnership allow. They are also interested in studying the drug in combination with other novel therapies to determine if broader clinical benefit can be achieved.

The other Northwestern co-author is Dr. Mary Mulcahy.

The study is titled, “Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.” It was funded by Actuate Therapeutics.

Mahalingam receives institutional research funding from Actuate Therapeutics and has received compensation for consulting from Actuate Therapeutics. Northwestern has financial interests in Actuate Therapeutics.

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