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Three-Pronged Immunotherapy Combination Shows Early Promise for Pancreatic Cancer

A mosaic of blue pancreatic cancer cells, surrounded by red membranes.
Credit: Min Yu/ National Cancer Institute/USC Norris Comprehensive Cancer Center
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Giving patients with operable pancreatic cancers a three-pronged combination immunotherapy treatment consisting of the pancreatic cancer vaccine GVAX, the immune checkpoint therapy nivolumab and urelemab, an anti-CD137 agonist antibody treatment, is safe, it increases the amount of cancer-killing immune system T cells in the tumors and it appears effective when given two weeks prior to cancer-removal surgery, according to new research directed by Johns Hopkins investigators. A description of the work was published online June 20 in the journal Nature Communications.


This study, led by researchers at the Johns Hopkins Kimmel Cancer Center, the Bloomberg~Kimmel Institute for Cancer Immunotherapy and the Johns Hopkins University School of Medicine, is the latest from an ongoing platform trial formed in 2015 to study immunotherapy treatments before surgery (neoadjuvant) and after surgery (adjuvant) for patients with pancreatic cancer. This format enables researchers to use data generated by the trial to advance development of immunotherapies for pancreatic cancer within the same study.


In this most recent part of the trial, 10 participants received the combination treatment. The median disease-free survival — the amount of time after treatment during which no cancer is found — was 33.51 months, and the median overall survival — time to death — was 35.5 months. These were higher than found in previous arms of the trial that tested the pancreatic cancer vaccine alone and in combination with nivolumab, but because of the small number of patients, the results did not have statistical significance.

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The tumor specimens studied in the recent arm also had much higher amounts of cancer-killing immune cells than specimens from patients given only the vaccine or the vaccine plus nivolumab.


The results suggest that this therapy combination warrants further study in a larger clinical trial, says senior study author Lei Zheng, M.D., Ph.D., co-director of the Pancreatic Cancer Precision Medicine Center of Excellence and professor of oncology at the Johns Hopkins University School of Medicine.


The platform trial has two purposes regarding pancreatic cancer treatments given during the two-week “window of opportunity” prior to surgery, Zheng says. First, it allows the immunotherapies to teach the patient’s immune cells how to respond to tumors, so they can continue surveillance later if the cancer recurs. Second, it enables investigators to see, by evaluating the tumors removed during surgery, how well the tumors respond to the treatment. A fourth arm of the trial, studying anti-interleukin-8 neutrophil-blocking antibodies in pancreatic tumors, is ongoing.


Reference: Heumann T, Judkins C, Li K, et al. A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. Nat Commun. 2023;14:3650. doi: 10.1038/s41467-023-39196-9


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