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Tackling Pancreatic Cancer with a Triple Threat

A novel immunotherapy-chemotherapy combination treatment shown to be safe and has potential to shrink pancreatic tumors

Advanced pancreatic cancer is notoriously resistant to available treatments – even immunotherapy. The cancer’s ability to evade the immune system remains one of the biggest challenges.

But that tough defense has also revealed new ways to attack it. An innovative approach that combines conventional treatments with the power of multiple immunotherapies to trigger an immune response is showing early promise for these patients. Laboratory data from the Abramson Cancer Center at the University of Pennsylvania successfully demonstrated that a novel three-pronged assault — a checkpoint inhibitor and an experimental CD40 antibody along with chemotherapy — could rev up the immune system to fight advanced pancreatic cancer.

To help move these encouraging results from the lab to the clinic with speed and efficiency, the Parker Institute for Cancer Immunotherapy assembled an interdisciplinary collaboration – including the nonprofit Cancer Research Institute, companies Bristol Myers Squibb and Apexigen, Inc., and all seven PICI academic research institutions – to study the treatment combination in patients. The phase 1b/2 clinical trial began enrolling patients in 2017 and was named PRINCE for Pancreatic Study Combining Nivo, a CD40 antibody and Chemotherapy.

The phase 1b analysis was published in The Lancet Oncology.

Data showed that while the immunotherapy-chemotherapy combination produced side effects in a majority of patients, they were manageable. Because of this, researchers were able to select a dosage of the experimental drug, the CD40 antibody (APX005M), for the next phase of the study – a primary goal of this portion of the trial.

In more than half of evaluable patients – 14 of 24 – the cancer shrunk in a clinically meaningful way, which is consistent with interim results presented at the American Association for Cancer Research annual meeting in April 2019. This effect lasted up to 16 months in some patients. And, more than two-thirds of patients lived beyond one year; whereas, the life expectancy of patients treated with chemotherapy alone is less than one year. The median overall survival was 20.1 months with at least 12 months of follow-up on all patients.

Early molecular analyses showed activation of the experimental CD40 antibody and an immune response in patients with the innovative regimen, consistent with a decade of lab investigation in mice conducted by senior author, Robert H. Vonderheide, MD, DPhil, a PICI investigator, member of the Cancer Research Institute (CRI) Clinical Accelerator leadership and director of the Abramson Cancer Center of the University of Pennsylvania.

“Innovation isn’t optional in pancreatic cancer,” said Dr. Vonderheide. “Because of PICI’s collaborative model, we were able to quickly test a cutting edge approach with the right investigators working together in synergistic ways. The robust data from this trial is already fueling new approaches of attack.”

The trial continues as a phase 2 study, already fully enrolled, evaluating the treatment’s efficacy in more patients. The team also seeks to further dissect the biology behind why pancreatic cancer resists treatment, and in particular, why the cancer resists immunotherapy.

“The PICI model is unique in that we leverage findings from our strong preclinical research model and combine it with an advanced translational and clinical strategy that is efficient and nimble. It means we can advance scientific learning faster for the entire field and, if needed, inform the next treatment combination more quickly,” said Ramy Ibrahim, MD, PICI’s chief medical officer.

PICI’s comprehensive translational platform will allow the team to provide advanced analytics to learn about how the drugs are working inside the body at the biological level. By leveraging in-house bioinformatics, bio-analytical expertise and tools across all seven sites through the translational platform, the collaborative can provide data needed for the field to create the next smarter strategy against cancer.

The team expects to deliver Phase 2 results in 2021.

Even as this trial progresses, the next trial is already in the works. The collaboration and data from the phase 1b trial have informed the design and potential patient selection for a new study that PICI aims to launch in 2021.