Dupixent for cancer? Researchers test blockbuster med as an immunotherapy-booster

Regeneron and Sanofi’s blockbuster Dupixent has conquered numerous anti-inflammatory indications. New research in mice now suggests that the monoclonal antibody could have a future as an immunology booster for lung cancer, too.

In a study published Dec. 6 in Nature, a research team led by scientists from the Icahn School of Medicine at Mount Sinai showed that pairing Dupixent with PD-1 inhibitors slowed tumor growth in mouse models of non-small cell lung cancer (NSCLC). In a small clinical trial involving patients with treatment-resistant NSCLC, all of whom were on either PD-1 or PD-L1 inhibitors, one patient saw his cancer disappear almost entirely. 

“80% of patients with metastatic lung cancer are going on to die from their disease, so we have to make some improvements,” Thomas Marron, M.D., Ph.D., senior co-author on the study, told Fierce Biotech Research. “And on top of that, most of the experimental drugs we give people are very toxic and have a lot of uncertainty, but dupilumab [Dupixent] has been given to hundreds of thousands, if not millions of people at this point."

Dupixent is a monoclonal antibody that blocks the immune pathways that make up the type 2 innate immune response, specifically those involving the cytokines interleukin-4 and interleukin-13 (IL-4 and IL-13, respectively). The drug got its first FDA green light in 2017 for use in treatment-refractory eczema. Approvals in asthma, chronic rhinosinusitis with nasal polyps, and the chronic disease eosinophilic esophagitis have since been added to the list. Sanofi and Regeneron plan to submit data for a COPD approval by the end of 2023. 

The therapy racked up a 33% increase in year-over-year sales in Q3 with $3.1 billion and is poised to become the first-ever biologic approved for chronic obstructive pulmonary disease, or COPD. 

The idea to test Dupixent with PD-1 inhibitors in NSCLC stemmed from earlier study results published in 2020. These assessments showed that the cancer was hijacking the systemic type 2 immune response—and specifically IL-4—in a way that turned it against immune checkpoint inhibitors, which rendered them ineffective in unleashing a patient’s T cells against their cancer. While there had been a bit of earlier research about the role of IL-4 in cancer, no one had pursued it as a target, Marron said. In general, the type 1 immune response is associated with cancer more than type 2. 

“It’s interesting because IL-4 is something that we classically think of as having nothing to do with cancer,” Marron said. “We think of it as having something to do with asthma and allergies and all the atopic conditions.” 

The scientists reasoned that blocking the type 2 immune response could “rescue” the response to PD-1 inhibitors. When they tested out the theory by blocking IL-4 in mice, they found that doing so not only slowed tumor growth in mouse models that typically had a slight response to immunotherapy but also those that usually did not respond at all.  

Based on these results, Marron concluded that it would make sense to see if Dupixent might have the same benefit in humans, given that it inhibits IL-4 and IL-13 and has an established safety profile. His team launched an independent clinical trial with six patients with treatment-resistant NSCLC who were taking PD-1 inhibitors. Each received three standard doses spaced three weeks apart, a more infrequent regimen than asthma or eczema patients typically receive, according to Marron. The primary endpoint for the trial was response rate at nine weeks. 

By the end of the study, biomarkers in all of the patients suggested that their immune response had shifted in favor of responding to PD-1 inhibitors.

“All of a sudden, we saw this very strong push toward the type 1 immune response, which is the anti-cancer response,” Marron said. The disease stabilized, at a minimum, in half the patients, though it continued to progress in the rest, he added. Marron noted that details on some of these individuals were not included in the paper but will be reported with data from a larger cohort at a medical conference next year.

Of the respondents, one case stood out: A patient whose cancer previously hadn’t responded to PD-1 inhibitors saw it nearly disappear after the three doses of Dupixent. He stayed on the immunotherapy drugs after the end of the study and his cancer continued to shrink. More than 17 months later, he remains in remission. These early results are encouraging, but there’s still much more work to be done. The researchers will need to figure out optimal dosing and learn who is the best candidate for the drug. The phase 2 clinical trial, which includes 21 patients and is underway now, will involve taking blood samples and biopsies so the researchers can hunt for biomarkers that might indicate who would have the best response.

“If I had to guess, this is not something that’s going to cure 100% of lung cancer,” Marron said. “I think that there’s probably a subset of patients where this really strong type 2 immune signature is the basis of their resistance to immunotherapy, and those are the patients that will benefit from the pill.”

Regeneron and Sanofi did not respond to a request for comment.