CRI Funded Scientists

Robert H. Vonderheide, MD, DPhil, Clinical Accelerator Investigator

University of Pennsylvania Abramson Cancer Center

Area of Research: Pancreatic Cancer

Dr. Robert Vonderheide is the John H. Glick Abramson Cancer Center professor at the University of Pennsylvania’s Perelman School of Medicine. He is the study chair of two pancreatic cancer clinical trials: “Safety and Efficacy of APX005M With Gemcitabine and Nab-Paclitaxel With or Without Nivolumab in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma (PRINCE)” (NCT03214250) and “A Phase 1b/2 Multicenter, Open-label, Exploratory Platform Study to Evaluate Immunotherapy Combinations for the Treatment of Patients with Previously Untreated Metastatic Pancreatic Adenocarcinoma (REVOLUTION)” (NCT04787991).

Roughly 460,000 people are diagnosed with pancreatic cancer worldwide each year, with 430,000 resulting deaths. 55,000 of those new cases and 44,000 of those deaths occur in the United States. The combination of no early symptoms with no widely used detection methods means that patients are often not diagnosed with pancreatic cancer until it has advanced to a very late stage.

The PRINCE trial examines various combinations of a checkpoint immunotherapy, an agonist immunomodulator, and chemotherapy in patients previously untreated metastatic pancreatic cancer. The checkpoint inhibitor nivolumab (Opdivo®) blocks the PD-1 pathway, whereas the agonist immunomodulator APX005M activates the CD40 pathway on antigen-presenting immune cells. The investigators will conduct extensive, deep immune profiling in order to determine if associations exist between the activity of certain immune cells and clinical benefits in patients.

Additional investigators working on this trial include:

  • George Fischer, MD (Stanford University)
  • Andrew Ko, MD (University of California, San Francisco)
  • Mark O’Hara, MD (UPenn Abramson Cancer Center)
  • Eileen O’Reilly, MD (Memorial Sloan Kettering Cancer Center)
  • Osama Rahma, MD (Dana Farber Cancer Institute)
  • Zev Wainberg, MD (University of California, Los Angeles)
  • Robert Wolff, MD (MD Anderson Cancer Center)

The REVOLUTION trial builds upon the PRINCE findings by testing additional drugs utilizing the same backbone in a platform setting. The study also incoprorates a unique cohort that explores cellular therapy in combination with immunotherapy. The goal of this cohort is to deepen ongoing responses in pancreatic cancer patients who have received chemotherapy and the anti-CTLA-4 drug ipilimumab by delivering antigen specific T cells along with ipilimumab to prolong and enhance response.

Additional investigators working on this trial include:

  • Andrew Ko, MD (University of California, San Francisco)
  • Cassian Yee, MD (MD Anderson Cancer Center)
  • Eileen O’Reilly, MD (Memorial Sloan Kettering Cancer Center)
  • George Fischer, MD, Ph.D. (Stanford University)
  • Mark O’Hara, MD (UPenn Abramson Cancer Center)
  • Osama Rahma, MD (Dana-Farber Cancer Institute)
  • Robert Wolff MD (MD Anderson Cancer Center)
  • Zev Wainberg, MD (University of California, Los Angeles)

Projects and Grants

Safety and Efficacy of APX005M With Gemcitabine and Nab-Paclitaxel With or Without Nivolumab in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma (PRINCE) (NCT03214250)

University of Pennsylvania | Pancreatic Cancer | 2017

A Phase 1b/2 Multicenter, Open-Label, Exploratory Platform Study to Evaluate Immunotherapy Combinations for the Treatment of Patients with Previously Untreated Metastatic Pancreatic Adenocarcinoma

University of Pennsylvania | Pancreatic Cancer | 2020

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