Cancer MoonShot 2020 is undeniably ambitious in its scope, timeline, and goals. First called for by Vice President Joe Biden last fall, the MoonShot initiative is broadly focused on “accelerating the potential of combination immunotherapies as the next generation standard-of-care in patients with cancer.”
The specifics easily match the overarching aspiration. The five year plan lays out a goal of conducting phase 2 trials in 20,000 patients across 20 different tumor types—and that's just in the first three years. Over the final two years, the MoonShot initiative hopes to move into phase 3 trials, with the ultimate goal of developing an effective immunotherapy-based vaccine against cancer by 2020.
BioPharma Dive spoke with Dr. Patrick Soon Shiong, the founder of NantWorks and a founder of the initiative, about how this impressive and challenging plan will get off the ground.
The dream team
Behind the 2020 goal is a powerful network of collaborators who have together formed the National Immunotherapy Coalition (NIC). Ranging from big pharma to biotech, members of the NIC include Celgene, Amgen, NantWorks, NantKwest, Etubics, Altor Bioscience, and Precision Biologics.
In addition, Independence Blue Cross, a major payer, has agreed to cover next-generation sequencing for patients with cancer. The vast scope of the trial program, with hopefully 20,000 cancer patients across several studies, requires a huge amount of genomic sequencing. Independence Blue Cross' coverage of the required sequencing will help address the costs.
25 years in the making
Some consider Cancer MoonShot 2020 to be aiming for an unrealistic goal. However, the structure of the MoonShot program is grounded in scientific reality, and a very hard-won reality at that, according to Dr. Soon-Shiong.
“This initiative is 25 years in the making, and is the result of a lot of work. It took a lot of time to assemble the necessary infrastructure to make this Cancer MoonShot a realistic goal, including everything from developing and refining the gene-sequencing process, to understanding genomics, proteomics, and how immune effector cells and tumors interact," he said.
Building on the strength of the National Cancer Institute’s network
When President Richard Nixon signed the National Cancer Act into law in 1971, the National Cancer Institute (NCI) received an influx of funding. The Act gave NCI money to establish 15 new cancer research centers, in addition to numerous local cancer-control programs and an international cancer research data bank. This significantly expanded the existing network of NCI cancer centers which had been funded by the government since 1960.
Fast forward four decades and there are now 69 NCI-designated cancer centers, across 35 states and Washington, D.C. These centers function as a nexus of collaboration between the biopharma industry, academic institutions, and government researchers. It is this network of NCI-designated cancer centers which forms the backbone of the Cancer MoonShot collaborative program, according to Soon-Shiong.
Ensituximab—a MoonShot target?
Just two weeks after President Obama introduced the Cancer MoonShot to the world in his State of the Union address, NIC member Precision Biologics announced positive phase 2 results from a trial involving its promising compound ensituximab, the first neoepitope 1-targeting antibody. The trial treated patients with refractory, metastatic colorectal cancer.
The research demonstrated ensituximab improved overall survival in heavily pretreated patients by 35%, compared with historical controls. In addition, 48% of trial patients showed stabilization of target lesions after two months of therapy.
A completely new target
But what makes this compound an appropriate candidate for a Cancer MoonShot-related study?
“The specificity of the target epitope makes ensituximab a good candidate for this program. Up to 60% of the patients screened for this study had tumor containing the target for ensituximab," Soon-Shiong explained.
Ensituximab is also being studied in pancreatic cancer, because the same epitope—or antigenic determinant—is expressed in certain pancreatic cancers.
Soon-Shiong pointed to the perfect matching of ensituximab with the epitope in question. “This is the first time that we have identified and targeted this epitope. Ensituximab is a perfect example of utilizing next-generation sequencing to identify new epitopes. We used tissue from patients with colon cancer and that allowed the researchers to determine that ensituximab had 100% specificity for that epitope, with no off-target effects,” he said.
Broadening the scope of immunotherapy
Cancer MoonShot shares some of the same breathtaking ambition as previous large-scale collaborative undertakings from the 20th century aimed at treating cancer. What’s new is the focus on immunotherapy and the tremendous opportunities unlocked by applying advanced profiling methods.
Cancer MoonShot 2020 represents the next wave of development in oncology therapy, buoyed by growing knowledge and better understanding of genomics and next-generation sequencing. It is also underpinned by also a whole host of new "omics", or molecular analysis fields: proteomics, epigenomics, transcriptomics, microbiomics, exposomics and metabolomics.
Promising treatment areas like checkpoint inhibitors and CAR-T have already made an impact on the oncology treatment landscape, and R&D is advancing at a rapid clip. However, this could be just the tip of the iceberg.
By using different profiling methods and improved data, researchers are now able to utilize multiple types of molecular analysis to address the heterogeneous nature of cancer in all its complexity, and to refine the targeting process.
From MoonShot to mundane
Prior to 1921, diabetes was a virtual death sentence for patients. Even with severe carbohydrate restriction and starvation diets, young patients would only live, on average three to four years, before slipping into a diabetic coma. They rarely survived to adulthood.
Then Dr. Frederick Banting and his colleagues at the University of Toronto “discovered” that insulin extracted from bovine pancreas could treat patients with type 1 diabetes.
Once insulin replacement became a mainstay treatment, a diabetes diagnosis became much less fatal.
Now when a child is born with diabetes, the ability to manage the disease is taken as a point of fact. While challenges remain, there is a rock-solid treatment paradigm in place.
In its Cancer MoonShot quest, the NIC is aiming to create a similar reality for cancer, where a diagnosis can be confronted with as much medical confidence as a diabetes diagnosis. In this way, cancer could become "curable," either through prevention or disease-management.