Overcoming Atezolizumab Resistance with Epigenetic Therapy in Urothelial Cancer

Dr. Peter A. Jones, PhD, DSc

VARI Chief Scientific OfficerVan Andel Research InstituteView Bio

Dr. Jones was born in South Africa, raised and attended college in Rhodesia (now Zimbabwe), and received his PhD from the University of London. He joined the University of Southern California in 1977, attaining the rank of Professor in 1985 and Distinguished Professor in 1999, and he was Director of the USC Norris Comprehensive Cancer Center between 1993 and 2011. His laboratory discovered the effects of 5-azacytidine on DNA methylation and linked this process to the activation of silenced genes. He is known for his studies on the molecular biology of cancer and of basic mechanisms of DNA methylation and its role in cancer and differentiation. He is a past President of the American Association for Cancer Research and was elected as a Fellow of the Academy of the AACR in 2013. He has published more than 300 scientific papers and received several honors, including the Outstanding Investigator Grant from the National Cancer Institute. He shared with Stephen Baylin the Kirk A. Landon Award for Basic Cancer Research from the AACR in 2009 and the Medal of Honor from the American Cancer Society in 2011.

Elizabeth Plimack, MD, MS

Fox Chase Cancer CenterChief, Division of Genitourinary Medical OncologyView Bio

Dr. Plimack is an Associate Professor of Medical Oncology, Chief of the Division of Genitourinary Medical Oncology and Director of Genitourinary Clinical Research at Fox Chase Cancer Center (FCCC). She is an expert on the treatment of genitourinary malignancies with a focus on bladder cancer. Her research effort is directed towards the discovery of novel therapeutic approaches and predictive biomarkers for patients with advanced bladder cancer. Dr. Plimack has extensive clinical trial experience with immunotherapies and novel combination therapies. She serves on the National Comprehensive Cancer Network guidelines panel for Bladder Cancer, the ASCO GU Scientific Program Committee, the Bladder Cancer Advocacy Network Think Tank Steering Committee, and on the American Joint Committee on Cancer (AJCC) Urinary Tract Expert Panel. Dr. Plimack received her undergraduate degree from Yale University and completed her M.D. degree and residency in Internal Medicine at the New York University School of Medicine. She went on to a Medical Oncology Fellowship at the MD Anderson Cancer Center, and received a Master’s in Patient Based Biologic Research from the University of Texas Graduate School of Biomedical Science.

View Full Team

Meet the Team

  • Peter A. Jones, PhD, DSc, Van Andel Research Institute
  • Elizabeth Plimack, MD, MS, Fox Chase Cancer Center
  • Stephen Baylin, MD, Johns Hopkins University/Van Andel Research Institute
  • Hui Shen, PhD, Van Andel Research Institute
  • Noah Hahn, MD, Johns Hopkins University
  • Scott Jewell, PhD, Van Andel Research Institute
  • David Quinn, MD, USC Norris Comprehensive Cancer Center
  • Jean-Pierre Issa, MD, Coriell Institute for Medical Research


  • Patient Advocate: Rick Bangs
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About This SU2C Catalyst Clinical Trial

Are you or a loved one currently facing bladder cancer? Stand Up To Cancer (SU2C) is supporting a clinical trial that may benefit patients with advanced or metastatic urothelial bladder cancer. This trial has the potential to make dramatic gains for future patient outcomes and survival of this disease.

Immunotherapies work by helping the patient’s immune system to help identify and fight cancer in the body. Currently, immunotherapies used to treat advanced bladder cancer are ineffective in approximately 75% of patients. This is because the immune system is controlled by “on” and “off” signals that tell the body when to attack and when to stand down. Cancer cells, however, can hijack this process, utilizing the “off” signal to stop the attack and effectively hide from the immune system.

What is epigenetic therapy?

Epigenetic therapy is the use of medicines to reprogram replicating cells to behave more like normal cells.

The goal of this trial is to help those patients whose cancers grow despite immunotherapy, by reversing their cancer’s resistance to immunotherapy (atezolizumab) by adding another type of treatment—epigenetic therapy (guadecitabine). The result, we believe, will be a one-two punch that is more effective than either approach has been on its own thus far.

We Need You

Why Your Participation Matters

Clinical trials are a critical step on the road to potential life-changing therapies; without them, new treatments for cancer cannot advance. Your participation in this trial will help move research forward by allowing us to test the benefits and effectiveness of the outlined combination therapy in the treatment of bladder cancer. It also has the potential to help inform future treatment approaches for other cancers as well.

Key Insights for Participants

• There is no guarantee that patients will benefit from this study. It is possible that your condition will improve, but it is also possible that there will be no effect or that your condition may continue to progress.
• All participants in this trial must agree to provide both biopsy and blood samples at the time of screening and through the duration of the study.
• This trial will test a combination of immunotherapy (atezolizumab) and epigenetic therapy (guadecitabine) in an effort to help reverse immunotherapy resistance in patients with advanced or metastatic urothelial bladder cancer.
• This trial will be conducted in two parts. Phase 1 will attempt to determine a safe and tolerable dose of the combination therapy. Phase 2 will evaluate the effectiveness of this combination therapy in patients with advanced bladder cancer.


Patients with advanced or metastatic urothelial bladder cancer are eligible to enroll. There are additional criteria that must be met to participate, or that may prevent a patient from participating.

Key criteria are summarized below and can be found in detail on Interested patients will need to review their medical histories with a clinical trial patient coordinator before they can be accepted to participate in this trial.

Male or female
Age Range:
18 years and older
Advanced or metastatic urothelial bladder cancer


Participants must have a measurable disease with at least one lesion that can be accurately measured.

Participants must have already received or been deemed ineligible for platinum-based chemotherapy and must have received at least one line of therapy with a PD-L1 or PD-1 targeting agent (such as atezolizumab or pembrolizumab).

Participants must have normal organ and marrow function.

Participants must have a life expectancy of at least 12 weeks.


You play a vital role.

Here are the locations where you can participate in this clinical trial. If you or a loved one are interested in enrolling and learning more about this study, please contact the patient coordinator at your preferred site. The patient coordinator is there to help you understand every aspect of the clinical trial process and can answer any questions you may have.

Once you contact the patient coordinator, he or she will start by reviewing your medical history with you to see whether you meet all the criteria to participate. The coordinator will then guide you through a review of the study and detailed “informed consent” documents that you are required to sign when you enroll in a clinical trial.

Philadelphia - Pennsylvania

Fox Chase Cancer Center, Lead Clinical Site
Patient Coordinator:
Manisha Saini
P: 215-214-1439

Los Angeles - California

University of Southern California
David I. Quinn, MD
P: 323-865-3956

Baltimore - Maryland

John Hopkins University Sidney Kimmel Comprehensive Cancer Center
Abby Asiama
P: 410-955-1168


Support for this trial comes from Genetech and Astex.
Learn more about Genetech +Learn more about Astex +
Here are some links to organizations that provide more information about advanced or metastatic urothelial bladder cancer and may also discuss patient support, treatment options, and current clinical trials.
Bladder Cancer Action Network (BCAN) +Urology Care Foundation +
For additional resources, please visit +

Find out if there's a trial for you. Reach out today.

Even if you do not meet the requirements for this trial, there may be other trials for you. Get started with the SU2C Clinical Trial Finder, a free and confidential cancer clinical trial matching and referral service.

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