LOS ANGELES—In October, Stand Up to Cancer (SU2C) awarded their first 10 SU2C Catalyst grants for trial projects in which researchers from more than 30 institutions collaborate across academic and corporate borders on clinical trials across a variety of cancers. The industry-supported program aims to correlate the research across these projects in hopes of better understanding why—not just if—certain treatments are effective, and will explore new uses for an array of powerful medicines.
The 10 inaugural clinical trials seek to address a wide variety of cancers, including breast, lung, melanoma, multiple myeloma, ovarian, pancreatic, hypermutant pediatric, sarcoma and urothelial. The Van Andel Research Institute (VARI) came away with two of these 10 grants for projects focusing on combination therapies in non-small cell lung cancer and bladder cancer.
Both VARI studies will work on pairing drugs that harness the immune system with epigenetic agents and moderate gene regulatory systems. Preclinical laboratory studies have suggested that altering certain epigenetic signaling in tumor cells may diminish their ability to evade the body’s immune response and help enhance the effects of immunotherapies. Non-small cell lung cancer and bladder cancer kill an estimated 173,000 combined people in the United States every year and tend to respond more favorably to immunotherapy than other cancer types.
The bladder cancer study, conducted at Fox Chase Cancer Center, University of Southern California in Los Angeles and Johns Hopkins University, was slated to open later this year. Supported by Genentech, a member of the Roche Group, the grant provides $2.9 million over three years for Van Andel Research Institute-Stand Up To Cancer (VARI-SU2C) Epigenetics Dream Team scientists to investigate whether guadecitabine (from Astex Pharmaceuticals) can flip critical epigenetic switches, reversing acquired resistance of bladder cancers to the immunotherapy drug atezolizumab (Tecentriq from Genentech). This resistance affects approximately 85 percent of all patients treated for the disease.
The lung cancer study, supported by Merck & Co. Inc. (known as MSD outside the U.S. and Canada) through a subsidiary for $2.5 million over three years, will combine two epigenetic drugs, guadecitabine (from Astex Pharmaceuticals) and mocetinostat (from Mirati Therapeutics), with the immunotherapy drug pembrolizumab (Keytruda from Merck). Rather than specific drug resistance, the goal of this trial will be to see whether epigenetic drugs can improve patient response to immunotherapies across the board. The trial is currently enrolling at Memorial Sloan Kettering Cancer Center in New York, with other sites expected to open in the coming months.
“The immune system is best known as the body’s protection against foreign intruders, such as viruses, but it can also recognize cancers,” says Dr. Stephen Baylin, co-director of the Cancer Biology Division and associate director for research programs for Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Director’s Scholar at VARI, co-leader of the VARI-SU2C Epigenetics Dream Team and co-leader of the lung cancer trial. “It is usually balanced by ‘on’ and ‘off’ signals that coordinate when to attack or retreat, but cancers can evade immune attack by commandeering the ‘off’ signal. We believe epigenetic modifications will be able to reverse this and help bolster the body’s immune response.”
The VARI–SU2C Epigenetics Dream Team, based at VARI in Grand Rapids, Mich., was established in 2014 and builds on the foundations laid by the first iteration of the SU2C Epigenetics Dream Team, which was founded in 2009. The team is led by VARI’s chief scientific officer, Dr. Peter Jones, and by Baylin. The team includes leading scientists and clinicians with vast experience in translating basic science and promising therapies from the lab to the clinic.
Stand Up To Cancer, which launched in 2008, is a program of the Entertainment Industry Foundation. This program draws on the resources of the entire entertainment industry to encourage the public to support research conducted by teams of scientists, as well as by individual investigators.
Grants to support the trials are being provided by the three charter supporters: founding collaborator Merck & Co., as well as Bristol-Myers Squibb Co. and Genentech.
“This unique industry-academic collaboration has reduced the time for SU2C to get clinical trials started by more than 75 percent while bringing significant scientific rigor to the selection and oversight of the projects,” stated SU2C President and CEO Dr. Sung Poblete. “SU2C actively manages these grants to minimize delays and support the achievement of key milestones.”
“Where companies often focus on an approval pathway for a specific indication, SU2C Catalyst broadens the approach by asking the scientific community how best to use the treatment in any setting and in any combination,” said Dr. Phillip A. Sharp, chairman of the SU2C Scientific Advisory Committee, an institute professor at MIT, a member of its Koch Institute for Integrative Cancer Research and a Nobel laureate. “These SU2C Catalyst projects promote combinations that would not likely be considered without this program even before they’re approved for other indications.”
“SU2C Catalyst has attracted excellent researchers to these problems who will couple the clinical trials with a significant amount of correlative translational research that immensely increases the value of this research,” he added.
Beyond industry and academia collaboration within SU2C Catalyst projects, data and outcomes are shared across the SU2C portfolio of 20 Dream Teams and also some half-dozen SU2C translational research teams that involve more than 140 leading cancer research institutions.
Distribution of grants as well as thorough and objective scientific oversight and review is provided by SU2C’s scientific partner, the American Association for Cancer Research.
“Immunotherapies have revolutionized cancer treatment by marshaling the body’s natural defenses to seek and destroy tumors, but tragically many patients eventually succumb to the disease as their cancer hijacks critical epigenetic signals and makes itself invisible to the immune system,” says VARI’s Jones. “We have great hope that this approach will help the body’s natural immune response recognize and destroy cancer cells.”
SU2C Catalyst grant recipients
In addition to the lung and bladder cancer studies at the Van Andel Research Institute (VARI), eight other projects were also awarded SU2C Catalyst grants, as follows:
- Translational Genomics Institute—$2.5 million to combine Merck’s Keytruda and AbbVie’s Zemplar in pancreatic cancer
- University of Washington and Dana-Farber Cancer Institute—$1 million to combine Keytruda and TESARO’s Zejula to study DNA repair therapies for ovarian cancer
- Dana-Farber Cancer Institute—$3 million to combine Bristol-Myers Squibb’s drugs nivolumab and lenalidomide in immunotherapy to prevent progression in multiple myeloma
- Duke University Medical Center—$2.5 million to study the use of Keytruda and radiation therapy in hopes of improving the outcome in high-risk sarcoma
- H. Lee Moffitt Cancer Center—$2.6 million to study nivolumab when used with Iovance Biotherapeutics’ tumor-infiltrating lymphocytes and Prometheus Laboratories’ IL-2
- The Hospital for Sick Children in Toronto—$2.99 million to study combined approaches by immune checkpoint inhibition for hypermutant cancers using Bristol-Myers Squibb drugs nivolumab and ipilimumab
- University of California, Los Angeles—$3 million to combine nivolumab and ipilimumab in an effort to reverse primary anti-PD-1 resistance
- Vanderbilt University Medical Center—$2.3 million to explorie immunotherapy combination strategies in ER-positive metastatic breast cancer with a triple combination of Genentech’s Tecentriq, Cotellic and idasanutlin.
For information on SU2C Catalyst and about these grants, visit http://progress.standuptocancer.org/catalyst.