The PRINCE Trial

Pancreatic cancer is notoriously ruthless. It strikes almost 60,000 people in the U.S. every year and is the No. 3 cause of cancer death in the nation. Unfortunately, the prognosis typically is poor.

For the subset of patients diagnosed with advanced metastatic pancreatic ductal adenocarcinoma (mPDAC), the disease studied in PRINCE, the five-year survival rate is less than 5%, according to the American Cancer Society.

Earlier clinical trials with immunotherapy alone failed against PDAC. 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

In 2017, PICI and its partners launched the PRINCE trial to evaluate a combination of chemotherapy, a checkpoint inhibitor and a unique antibody. Enrolling at remarkable speed, researchers presented early results less than two years later, showing that the combination has the ability to shrink tumors.

Our dedicated collaborators then helped successfully transition the trial to Phase II, open to patients with untreated mPDAC. Here, we evaluated the combination of standard-of-care chemotherapy (gemcitabine + nab-paclitaxel) and nivolumab, a PD-1 inhibitor, and/or sotigalimab, an experimental antibody that is an agonist of the CD40 protein.

PICI researchers uncovered various predictive biomarkers associated with longer overall survival for certain patients with mPDAC.

Treatments Tested

• APX005M
• Nivolumab
• Gemcitabine and nab-paclitaxel

Results

The promising findings were published in Nature Medicine and presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, both on June 3, 2022.

As part of exploratory analyses, researchers discovered distinct biosignatures associated with longer survival for the nivolumab-chemotherapy and sotigalimab-chemotherapy treatment arms, which reflect each immunotherapy’s unique mechanisms of action.

These biosignatures could be the first step towards developing prospective tests that can be used to determine which patients will benefit most from which chemoimmunotherapy regimens. This could lead to clearer treatment plans and real outcomes for pancreatic cancer patients through immunotherapy.

Where We’re At Now

The data suggest the treatment regimens may not be appropriate for all PDAC patients. However, the predictive biomarkers that appear to correlate with longer survival for some patients warrant further study. Chemoimmunotherapy combinations may improve outcomes for some patients with metastatic PDAC.

Following up on these results, the scientific community can work to better understand who is most likely to benefit, and why.