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The PRINCE Trial

Pancreatic Cancer: Can a Combination of Immunotherapy and Chemotherapy Defeat It?

Why This Trial

Pancreatic cancer is notoriously ruthless. It strikes almost 60,000 people in the United States every year and is now the third leading cause of cancer-related deaths in the nation. Only 8.5% of patients survive five years after diagnosis.

Pancreatic ductal adenocarcinoma (PDAC) is the most common form.

Earlier clinical trials with immunotherapy alone failed against this type of cancer. However, research by PICI investigator Robert Vonderheide, MD, DPhil, of the University of Pennsylvania suggested that combining immunotherapy and chemotherapy showed promise for defeating this disease.

About the Study

We tackle pancreatic cancer from different angles in this trial, now in phase 2. In addition to standard-of-care chemotherapy, we attack the tumor with two different immunotherapy agents.

One is an experimental antibody that targets the CD40 protein and propels the immune system into action. The second is a PD-1 checkpoint inhibitor that takes the brakes off the immune system so it can fight cancer more effectively.

Who Was Eligible

  • The trial was open to patients with untreated metastatic pancreatic ductal adenocarcinoma.

Treatments Tested

  • APX005M
  • Nivolumab
  • Gemcitabine and nab-paclitaxel


Promising interim phase 1b findings were presented at the 2019 American Association for Cancer Research annual meeting. Phase 1b safety and biomarker analysis was published in The Lancet Oncology in January 2021.

The novel treatment combination shrank pancreatic tumors in more than half of evaluable patients. More than two thirds of patients remained on treatment for a year or more, indicating that the combination was capable of inducing long-lasting responses; whereas, the life expectancy of patients treated with chemotherapy alone is less than one year. This is the first demonstration that immunotherapy can have a positive effect in pancreatic cancer.

Phase 2 results were presented at the 2021 American Society of Clinical Oncology 2021 Annual Meeting.

The study found the combination of chemotherapy nivolumab – a combination not previously thought to be effective – improved overall survival compared to historical data for chemotherapy alone. The study also found adding a CD40 agonist to chemotherapy can activate dendritic and B cells in pancreatic cancer patients, key components of the immune response.

Where We’re At Now

The first patients underwent treatment in August 2017 at the University of Pennsylvania.

After a successful phase 1b trial, we completed enrollment for phase 2 in June 2019. Our researchers presented those results at the ASCO 2021 annual meeting.

Based on data from this trial, a platform study is in design to test science-driven novel combinations.



Site Investigators

  • George Fisher, MD | Stanford Medicine
  • Andrew Ko, MD | University of California, San Francisco
  • Mark O’Hara, MD | University of Pennsylvania
  • Eileen O’Reilly, MD | Memorial Sloan Kettering Cancer Center
  • Gauri Varadhachary, MD | The University of Texas MD Anderson Cancer Center
  • Zev Wainberg, MD | University of California, Los Angeles


Leveraging our collaborative model, we engaged partners in academia, biotech, pharma and nonprofit to make the trial a reality, going from concept to launch in less than six months.

PICI holds the Investigational New Drug application from the U.S. Federal Drug Administration.

For more information on this trial (NCT03214250), visit