publication date: Apr. 1, 2016

NCI Makes Plans for Moonshot Dollars 

 

At a meeting of the NCI Board of Scientific Advisors March 29, NCI officials had good news to report:

• The appropriations are increasing, with bipartisan support to boot.

• The White House “moonshot” initiative on cancer is bringing new money and new urgency to the institute’s work.

The cancer program has seen many aggressive mandates and has made many big promises, and it’s worthwhile to remember this current initiative is being launched by an administration that is concluding its term.

The resources being placed on the table will flow through the relatively simple bureaucratic machinery that will be largely housed within NCI.

The institute is about to announce the members of a “blue ribbon” panel that will guide its moonshot efforts.

Though initial funding is relatively modest by comparison with the overall federal spending on biomedical research, the moonshot is shaping up as a broad-based research and public health initiative.

The administration’s $1 billion proposal establishes a game plan for how the funds will be spent: the moonshot initiative will begin with $195 million in cancer research at NIH in fiscal 2016, according to the White House.

The budget for the 2017 fiscal year proposes to allocate $755 million in mandatory funds for new cancer-related research activities—$680 million for NIH and $75 million for FDA. The remaining $50 million is expected to fund Centers of Excellence in the Departments of Defense and Veterans Affairs. (The Cancer Letter, Feb. 12.)

“The overall goal is to accelerate progress in cancer, including prevention and screening, to go from cutting-edge basic research, all the way to greater uptake of the standard of care,” Lowy said to BSA. “It’s to encourage cooperation and breaking down siloes, both in and between academia, government and the private sector, and the overriding importance of data sharing.”

Lowy said the new money will speed up progress.

“Needless to say, the proposed amount of money is just a small proportion of what the NCI has,” Lowy said. “In addition, there’s a lot of additional investment in cancer research. So this is just on top of what’s already being done. We are going to try to coordinate the rest of the research so that putting them together, we will be able to make faster progress.

“The money allocated or being proposed for the initiative by itself is not going to change things overall, because although it’s a lot of money, relative to all the other investment, it’s relatively small.”

In June, NCI will provide greater detail on the Genomic Data Commons, which will enable the sharing of annotated patient-level clinical and cancer genomic data.

“One of the charges in the president’s memo establishing the cancer initiative was to try to accelerate research so that what would normally have been done in a decade could be done in five years,” said Dinah Singer, director of the NCI Division of Cancer Biology, who was recently named NCI acting deputy director. Warren Kibbe, director of the NCI Center for Biomedical Informatics and Information Technology, was also named acting deputy director. 

Likely, NCI would be able to move quickly to distribute the money.

For example, the moonshot will include an “exceptional opportunities fund.”

“This fund is slated to have up to $100 million in it, and the idea is if new and exciting ideas emerge…, that fund could be used in a very rapid way to support various groups to pursue the research in that area,” Singer said. “One could imagine, for instance, launching challenges that would be open to the broader community that could be relatively quickly funded.”

The following are excerpted presentations by Lowy, Singer and James Doroshow, NCI deputy director and director of the NCI Division of Cancer Treatment and Diagnosis:

 

LOWY: There is the potential for continuing increases in federal cancer research funding, and for NIH funding, and it’s important that this funding is frequently coordinated with private funding efforts. For example, today there’s going to be an announcement of a $125 million donation by former New York City Mayor Bloomberg and Sidney Kimmel and others to Johns Hopkins, and this is just one area of private philanthropy making private contributions for cancer research.

For FY16, the NCI received about $265 million in a total increase—$70 million was for the president’s Precision Medicine Initiative in oncology, and we have gone over the elements of that effort previously. As I mentioned, Jim will say a little bit about a couple of areas. And $195 million was for non-PMI oncology activities.

I just want to focus on one aspect for the current fiscal year. We are adding about $50 million to the non-competing awards, the Type 5 awards, because that enables us to continue support at the 100 percent commitment level. In addition, we are adding about $53 million for the new and competing awards—those are the type 1 and type 2 awards. The rationale for that is that about $447 million became available for FY16 from the awards that were ending. So we are supplementing that with $53 million, so that when it comes to these awards, we will be at approximately the $500 million level.

[Consider] the funding for the NCI for the last almost 20 years. There have been substantial changes. The increase in FY16, note that this is really just keeping pace with inflation. But there’s a substantial increase proposed for FY17 of $680 million for the NCI by the president’s budget. And this would go ahead of inflation and get us at about the same purchasing power as 2000-2001, sort of in the middle of the doubling.

I’d like to turn now to the vice president’s cancer initiative, of which there has been a fair amount written, but not too many specifics up to now.

The overall goal is to accelerate progress in cancer, including prevention and screening, to go from cutting-edge basic research, all the way to greater uptake of the standard of care. It’s to encourage cooperation and breaking down siloes, both in and between academia, government and the private sector, and the overriding importance of data sharing.

In June, NCI is going public with the Genomic Data Commons, and this will enable annotated patient-level clinical data, and omics—and as you will hear when Warren [Kibbe] talks about it in more detail in June, there will be an opportunity for others who wish to contribute such information to the genomic data commons, that it will be able to accommodate that. This information will be publicly available to the scientific community.

Many people are aware that the vice president’s initiative is referred to as the moonshot, and there has been a certain amount of controversy about what that implies. During a visit of the vice president to the University of Pennsylvania Abramson Cancer Center in January—these are two quotes, just so that he understands that this is not going to be a single magic bullet, or landing on a particular crater on the moon, that is going to take care of everything. He says, we’re talking about prevention, early detection, “I’m convinced that we can get answers and come up with game-changing treatments and get them to people who need them. We have the opportunity to fundamentally change the trajectory.”

The scientific proposal is going to be vetted by the blue ribbon panel, which we hope will be announced in the very near future, perhaps this week, this will be an evaluation of the current proposal and their recommendations which will be made to the NCAB may or may not look like what I am discussing now.

One of the proposals is to develop preventive interventions, such as vaccines against infectious and non-infections targets. These different proposals take advantage of recent technological innovation, and try to apply these advances in different areas of cancer research. The one area is with the [Epstein-Barr virus] vaccine—we had the presentation from Jeff Cohen [chief of the Laboratory of Infectious Diseases and the Medical Virology Section at the National Institute of Allergy and Infectious Diseases] back in December—but also trying to think about immunological approaches to deal with precancers or early invasive cancer that might be able to be targeted when there are not—to molecular abnormalities, that have nothing to do with infections.

[Other proposals to] develop screening tests with bodily fluids, and there has been a lot of publicity about blood, but also urine, saliva, and other fluids. There have been enormous improvements in sensitivity and specificity particularly with identifying nucleic acids, which are currently being used to monitor recurrence of cancer, etc., but there is some potential to use this as a screening test. And then increased uptake of standard of care for prevention screening, as well as for treatment.

[Proposals in] cancer treatment, in clinical and preclinical work, to increase immunotherapy trials and combination therapy trials, increase patient participation in clinical trials, develop new treatments for pediatric cancer, develop a drug formulary for many companies, but that formulary would be at NCI to facilitate the study of combination therapy and other activities, and Jim will talk about that during his remarks.

And, importantly, to expand the omics analyses of tumor cells and stromal cells for patients and also to include clinical annotation that would be far better than what has been available through TCGA.

And then some other areas, as I mentioned, increasing preclinical vaccines and cancer immunotherapies, increase basic research, especially in immunology, and to develop exceptional opportunities fund for new opportunities in cancer research.

I’d now like to turn the discussion over to Dinah, and she will continue to talk about the vice president’s initiative.

 

SINGER: The cancer initiative was announced by President Obama in his State of the Union message back in January. The idea was to accelerate progress in cancer. And it really is to extend all the way from basic research in cancer through translational and clinical and also access to care. So it is a very broad-spectrum initiative that is intended to really affect patients.

Specifically, it’s also going to encourage greater coordination and collaboration. There’s a sense in the White House of siloes that exist within academia and within government and within the private sector, and between them all. One of the goals is to break down those siloes and finally to enhance data sharing, which Doug also alluded to a little bit.

To give you an idea of how this whole initiative is structured, the presidential memo that established this initiative places this leadership directly in the White House, with the vice president, in his office.

Derived from that is a federal task force for the cancer moonshot, which includes the NCI and the NIH, and, within the presidential memo, creates a blue ribbon panel, which is a working group of the NCAB, and authorizes the blue ribbon panel to form working groups to further pursue the science to make recommendations back to the blue ribbon panel—which will report back to the NCAB, which will report back to the NCI director, who, through the NIH, will report back to the federal task force the recommendations for the scientific opportunities.

The federal task force met here back in February. It was attended not only by Vice President Biden but also by President Obama—and it might not be immediately apparent, but the leaders of the free world were looking to Doug for advice.

The task force consists of about 13 federal agencies. This is only a partial listing. The vice president is chair. The secretary of HHS is on the task force, representatives for NCI—you’ve already saw Doug—Jim was actually there, but he wasn’t in that picture; he’s also in another one. They were also looking to Jim for leadership.

NIH, FDA is represented; Commerce and the Patent and Trademark Office is involved; the Department of Defense and the Veterans Administration; the Department of Energy, and NSF, and a few others are all part of this task force.

Reflecting on the goals of the moonshot initiative, the specific identified goals of the task force again are to accelerate our understanding of cancer, its prevention, early detection, treatment and cure—importantly to support greater access to research data and computational capabilities.

Improving patient access to care is another important component of the moonshot mission. To identify and address any barriers and to consider any ways to expedite considered reforms and to identify opportunities to develop public-private partnerships to increase coordination of the federal government’s efforts with the private sector as appropriate. Obviously the first two bullets are where NCI has the greatest responsibility.

The task force will also be looking at ways to improve patient access and care. The FDA is already starting to think about ways to reduce regulatory barriers. And Francis Collins has already tried to establish some new public-private partnerships in this arena.

One of the attempts to progress the cancer research that was specifically mentioned in the president’s memo was the establishment of a blue ribbon panel, which is going to be a working group of the NCAB, and the goal or the charge of the blue ribbon panel is to provide expert advice on the vision and proposed scientific goals and implementation of the national cancer moonshot. Importantly the panel is authorized to recommend other cancer research activities to enhance this effort.

As Doug mentioned the roster of the panel has not been released yet officially, but we anticipate that it’s not going to be more than about 20 people, which is really not enough to provide all the scientific expertise that would be needed to really provide or identify the various important opportunities and gaps that should be addressed through this cancer initiative.

The panel is authorized to establish working groups, and we anticipate that this will be one of the first actions of the panel, focused on the various scientific themes that the panel thinks are going to be of critical importance to pursue and provide feedback and recommendations.

In the original proposal that went to the White House, these areas were identified, Doug went through the science in many of these, and we anticipate that these will be among the areas that the working groups will be asked to evaluate, so again: cancer and prevention vaccine development, not only for infectious agents, but also for the non-infectious agent vaccines; detection is going to be a critically important component of the effort; cancer immunotherapy and combination therapy; genomic analysis of tumor and surrounding cells, I think with an important emphasis on the surrounding cells, but also on the stromal components and secreted factors. Enhanced data sharing has been a topic of discussion here and beyond, and I think will be a major focus that Warren will talk about. New approaches to pediatric cancer, understanding the underlying molecular bases, and new therapeutic options, and the exceptional opportunities fund.

This fund is slated to have up to $100 million in it, and the idea is if new and exciting ideas emerge from all of these considerations, that fund could be used in a very rapid way to support various groups to pursue the research in that area. One could imagine, for instance, launching challenges that would be open to the broader community that could be relatively quickly funded.

Now, critical to a successful accomplishment, the identification of scientific goals is trying to get as much input from the broader scientific community, the patient and the advocacy community, and the public at large. We’ve begun to formulate a strategy for scientific outreach, with the goal of providing the public and experts who are not engaged in the blue ribbon panel or in the working groups with ways to submit their ideas or proposals, and also to try to increase the public’s participation and engage the broader public in the development of scientific opportunities.

And so the approaches that are being considered are an online idea repository, where people would post their proposals for new ideas—also we’d be willing to accept new ideas by email. We’d have workshops in a variety of different areas.

There’s going to be representation of the NCI at various professional meetings including AACR and ASCO. And we also hope to have some of the blue ribbon panel meetings open to the public, as well as the working group, so we hope in that way to not only receive information but also to be very transparent in the [deliberations] of the panel and the working groups.

One of the charges in the president’s memo establishing the cancer initiative was to try to accelerate research so that what would normally have been done in a decade could be done in five years. Accordingly, there’s a very aggressive timeline for the blue ribbon panel to complete its work. What we are hoping is that by the August-October 2016 timeframe we will already be preparing FOA concepts that will be brought here for approval and then publication with the goal of actually funding awards in the summer of 2017.

 

DOROSHOW: One of the aspects of the moonshot activities builds on something that’s not really terribly expensive in dollars, but is expensive in terms of time, regulatory effort and interactions that need to be established.

Many of you know, I’ve talked a little about how we have a timeline for the development of the MATCH trial, and the length of time that it took to develop the formulary for the drugs involved in that study—roughly two years of negotiations with a large number of pharma companies that was reflected in a study that will reopen in a month or two with 24 different drug arms.

But all of those agreements, all the CRADAs, clinical trials agreements etc., are all related to a single clinical trial. And over the same two years, maybe longer timeframe, I’ve had many discussions—not only with folks around this table, but with many of the NCI cancer center directors—about how we could potentially help them to enhance their own precision medicine activities at their own centers.

Many months ago, actually, even before the moonshot activities got off the ground, but certainly catalyzed thereafter, we’ve begun trying to develop a process of developing a virtual drug formulary that we could make available for studies at individual NCI-designated cancer centers, and other centers that could hold their own in investigator-initiated INDs, but where we would serve to distribute drugs which is a relatively costly process—do some overall quality control and facilitate the IP arrangements with a large number of companies.

I can tell you that we’ve spoken to a number of companies so far, and have had a number of calls scheduled for the next several weeks, and pretty much the response has been positive. Always the details are the issue, but we hope to have a large meeting at ASCO with many pharma companies there because we want to be able to provide as many drugs as possible to all of your centers for all the studies that you would all like to do, whether they’re supported by NCI grants or your own philanthropic or other kinds of funds.

I know especially for combination studies, utilizing drugs from two different companies—as well as for preclinical activities, but primarily for clinical trials, this has been a major limiting issue that has made it difficult for centers around the country to carry through their mission.

We hope to roll this out as part of the moonshot activity. One of the encouraging parts of this is that we have strong support from the vice president’s office. He is certainly willing to interact with pharmaceutical companies to try to facilitate access to these compounds for such trials.

So, more later—it’s certainly something that is in process—but we would love to have, by the end of the year, something that we can announce to you.

Let me give you a little bit of update on the precision medicine activities, because you will be seeing—both at the June meeting and at subsequent meetings—RFAs that come to you that are in response to the funding from the precision medicine in oncology activities.

The first of these will be in the area of immunotherapy. We were very fortunate to have a large workshop toward the end of January—very well attended, with outstanding presentations that generated a plethora of ideas. The only issue will be how much money we have to carry forward these ideas.

Just to give you broad brushstrokes, because of course you will see the details: but there was a lot of support for trying to fund more in the way of basic immunotherapy, in the R01 space.

There was significant interest in the NCI trying to support further development and pilot activities in the T cell adoptive immunotherapy, which is a very expensive undertaking, as you all know. And then I think the largest amount of support was for us to work with the immunotherapy community to figure out how we could develop platforms to take the clinical trials that we’re supporting—not just to do more trials that companies might be interested in doing, but rather to have the kinds of correlative science translational support to really understand inpatient materials, biopsies, pretreatment biopsies and the like and circulating cells, and the pharmacodynamic effects and molecular effects of these compounds are in the context of both tumor and stromal cells.

And that’s an expensive undertaking, but there are organizations, many of them at your institutions, well poised to facilitate the fairly large spectrum of immunotherapy trials that the NCI supports now, without that kind of basic scientific translational scientific underpinning that we would hope to be able to utilize some of these funds to carry forward. And you will hear more about this at the next meeting.

There are other activities related to PMO that are in the process of development. We’re having a workshop on Thursday about patient-derived xenografts. You will almost certainly see FOAs related to that activity, but with respect not to phase, but to the associated development of the NCI’s PDX repository.

I’m happy to tell you that it’s very likely that, come July or so, we will be open for business in terms of starting to distribute the first cell lines and models that we will make available at very modest cost—very well-characterized models.

Our website will go live—and you’ll all get notice of this; this is not something that will be under the radar. We are all working very hard to make sure that we have enough material to supply your investigators when this goes live in July.

Copyright (c) 2017 The Cancer Letter Inc.