publication date: May. 20, 2016

NCI Identifies Moonshot Priorities 


NCI is working to provide five to ten recommendations for Vice President Joe Biden’s cancer moonshot program, officials said at a recent advisory committee meeting.

At a meeting of the Frederick National Laboratory Advisory Committee May 11, top NCI officials described the mechanisms that will be used to provide recommendations for spending new money that may be directed at cancer research.

The institute’s Blue Ribbon Panel—consisting of 28 members representing academia, government, industry and patient advocates—has assembled seven working groups to focus on the following categories:

• Cancer immunology and prevention,

• Tumor evolution and progression,

• Precision prevention and early detection,

• Expanding clinical trials,

• Pediatric cancer,

• Enhanced data sharing, and

• Implementation sciences.

Each 10 to 12-member group is expected to provide two to three recommendations identifying scientific opportunities for acceleration.

These recommendations will be submitted to the Blue Ribbon Panel, which will vet and synthesize the suggestions before sending the final working report to the National Cancer Advisory Board for its consideration (The Cancer Letter, April 8). The report is expected to be submitted to NCAB in August.

The update was presented to the Frederick National Laboratory Advisory Committee, which provides oversight for administrative and research activities at the Frederick National Laboratory for Cancer Research.

At $400 million, the laboratory is one of the largest of the nation’s 42 Federally Funded Research and Development Centers.

As the institute prepares to re-compete FNLCR’s contract later this year, NCI officials see the process as an opportunity to:

• Assess the FNLCR’s potential for contributing to big-picture, larger goals in oncology, including the goals set out in the National Cancer Moonshot Program.

• Review how federal funds are used at the laboratory,

• Select a contractor that can best meet the most “urgent needs” of the institute, and

• Focus FNLCR resources towards conducting research that would be difficult to perform elsewhere.

“With the FNLAC and the Frederick National Laboratory, we really focus on the work that you conduct and coordinate—research that would be difficult or less efficient to carry out by other mechanisms,” said NCI Acting Director Doug Lowy to committee members May 11. “The FNLAC committee is key for helping to guide us on this.”

Though initial funding from Vice President Biden’s initiative 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.

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).

“It’s really been a whirlwind, but I think we’re really making progress,” said Dinah Singer, a co-chair of the Blue Ribbon Panel, NCI acting deputy director, and director of the NCI Division of Cancer Biology. “I really expect that we’re going to have all aspirational recommendations coming out that are actually feasible to actually attain in a period of one to five years.”

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


LOWY: I would like to start this morning by telling you about a number of different activities that are ongoing at NCI, some of which are directly relevant to the Frederick National Laboratory, but most of which are really more NCI-wide activities.

I would first like to set the stage for what I think is going on in cancer research today. I think that there are many opportunities to accelerate progress in virtually all areas of cancer research and we are fortunate to have public optimism about the future of cancer treatment that it can beneficial for more patients and less toxic.

While we applaud the optimism, we must go beyond treatment for maximum progress and in addition, we must not overpromise. To maximize progress, we must support research in many areas and these include basic research, etiology, pathogenesis, prevention, screening, treatment, and survivorship. We should also recognize the importance of implementation research, and disseminating what we already know works. This is to improve cancer health by increasing standard of care uptake and promoting healthy lifestyle.

I think our progress is going to be measured in several different ways. Of course, advancing understanding of cancer, preventing it, screening for it, treating it, and improving quality of life after a cancer diagnosis are critical to the research that we do. And it really is the ongoing importance of continuing to do what has never been done before.

In addition, I think that we will be asked, “What is happening overall with cancer mortality rates, including specific cancers?” Finally, we will need to attract and retain high quality young investigators.

I have two slides about cancer mortality rates, not that you need them, but to make sure that when you talk about what happens in cancer, that you highlight for people not in our area that cancer mortality rates really have been going down. Particularly for women, in the 10-year period between 1994 to 2003, it went down by just 7 percent, whereas they went down by 12 percent in the most recent decade.

It’s important to recognize that cancer mortality rates are going down for the vast majority of cancers. Of course, we are still dealing unsuccessfully with liver cancers when it comes to treatment, and also with pancreatic cancer. But there are some people who assert that the only reason that we have decreases in cancer mortality is because of decrease in tobacco consumption, and that’s simply wrong. The decreases that we see in mortality rates are attributable to a combination of prevention, screening, and treatment.

Here, with the FNLAC and the Frederick National Laboratory, we focus on the work that you conduct and coordinate—research that would be difficult or less efficient to carry out by other mechanisms and the FNLAC committee is key for helping to guide us on this. And the RAS initiative—and you will be hearing yet another aspect or iteration of the RAS initiative later this morning—exemplifies some of those initiatives.

There are many projects that use state-of-the-art technology or develop critical reagents to help address important cancer research problems. At the last meeting of the FNLAC, you recommended establishing the cryo-EM user facility at the FNL and the Titan Kronos microscope has been delivered and is being installed. We plan to open the user facility in the fall of 2016. Sriram Subramaniam [head of the Biophysics Section of the NCI Center for Cancer Research] will be in charge of it, but he is forming a steering committee, which will include one or more members of the FNLAC as is only appropriate.

Specific topics this morning: I’d like to talk briefly about the NCI budget outlook, which I think for the first time in a long time is positive for the current fiscal year and is also positive as proposed for FY2017.

We’ll then talk about the vice president’s cancer initiative, and Dinah Singer will be doing that, because she has really taken the lead in coordinating this cancer initiative. The initiative includes cutting edge research as well as increasing the uptake of standard of care, and to increase collaboration and sharing, and decrease administrative and regulatory barriers. You’ll be hearing, for example, about some of the Department of Energy cooperative projects that we are doing, which are very much along these lines.

There is strong bipartisan support for NCI and NIH, thanks to advocates of many kinds. Last year, the NIH received an increase in its appropriations for the first time, really, in more than 10 years, and we received a 5 percent increase. This will enable faster progress for understanding cancer and for our patients. There is potential for continuing increases for 2017 and importantly, coordination with private funding efforts. The private funding efforts really have to do with philanthropy, where private philanthropy clearly leverages the support that NCI is able to give.

This slide [above] shows you the budget for NCI since 1998. The light blue represents absolute dollars and in the dark blue are the dollars with cost of living adjustment. These green areas are the ARRA funding or stimulus. I hope you can see that even if we get the proposed appropriations for 2017, it will basically put us where we were, in the middle of the doubling between 2000 and 2001, but at the moment, we’re really more after the first year of the doubling. The proposal for 2017 is a 13 percent increase to the NCI, and we think there are ample reasons to justify the confidence that the administration has placed in the opportunities that we currently have in cancer research.

So where have we put the [$265 million increase] for this fiscal year? Of the rest of the money, we have taken about a little more than half and put it into investigator-initiated research so that we can fully fund the Type 5 non-competing awards and also fund substantially above the money that is turned over as a result of the ending of awards. We also have already increased the cancer center support grants by $10 million in this fiscal year, which has increased the base levels for 21 of the 69 grants, and we are committed—regardless of whether or not there is an increase for FY17—to add another $30 million, so that when cancer centers come in for their renewals, if they score well, all of them will be able to get an increase in their award, and we also have had some overhead and inflation cost.

I now turn to the topic of the vice president’s cancer initiative, otherwise known as the moonshot. The goal is to:

• Accelerate progress in cancer, including prevention and screening, from cutting edge basic research to wider uptake of standard of care,

• Encourage greater cooperation and breaking down of silos, within and between academia, government and the private sector, and

• Emphasize the importance of data sharing with the Genomic Data Commons, which is coming online next month, being front and center for this.

There is, I think, an unintentional communication that cancer is now mainly a technological or engineering problem. And I think that terms such as “precision medicine” may inadvertently imply understanding that is greater than actually is, and that advances in cancer no longer depend on scientific discovery of the unknown. In addition, we talk about immunotherapy and immune checkpoint inhibitors, or chimeric antigen receptors, it’s based on understanding of immune regulation, but we all know that there’s still much that we don’t understand. I think it’s important for us as we talk about the opportunities in cancer research to emphasize that progress in cancer remains heavily dependent on developing new knowledge.

The vice president’s cancer initiative is really an opportunity for focused research to accelerate progress. It will take advantage of current advances in the understanding of cancer and recent technological innovation, and applying that knowledge and innovation to focus on specific projects that can have a substantial impact on understanding or improvement for patients. But it’s really important to recognize that NCI will continue to support a great deal of other meritorious research, and while many eyes are focused on the vice president’s initiative and the activities of the Blue Ribbon Panel, it’s really important to remember that NCI is not only going to continue supporting what we’ve been supporting, but also to have new initiatives that may well fall outside out of the vice president’s initiative.


SINGER: Thanks, Doug, for introducing the initiative. It was launched at President Obama’s State of the Union, where he announced a major initiative and called it a “moonshot” to advance cancer. He named Vice President Biden as the lead for that initiative and has assembled around Vice President Biden a task force that is charged with developing all of the areas that will advance our understanding of cancer, and that is not limited just to cancer research, but also health care delivery, access to care, and policy barriers.

Within the task force, NCI has been charged through our National Cancer Advisory Board with forming a Blue Ribbon Panel, which is supposed to really look into the scientific opportunities that could be accelerated through this initiative.

The presidential memo appointed Vice President Biden as the chair of the task force and named 13 federal agencies as members of the task force, with the department heads being named to serve on it—NCI, NIH and FDA, as well as HHS, are all represented. There was initially a total of 13 agencies, I think it’s now been increased to 15 or 16 agencies who are interested in participating.

The goals of the task force—the parent panel—are to:

• Accelerate our understanding of cancer, it’s early detection, prevention, treatment, and hopefully cure,

• Support greater access to new research, data, and computational capabilities,

• Improve patient access and care,

• Identify and address any unnecessary regulatory barriers and consider ways to expedite administrative reforms, and

• Identify opportunities to develop public-private partnerships and increase coordination of the federal government’s efforts with academia and the private sector.

So clearly, our mission within the NCI and NIH falls into this bullet and second bullet. The remaining bullets rise to the level of the task force, because they are not specifically focused on science and research.

Within the task force, a Blue Ribbon Panel has been organized. It has 28 members that represent a spectrum of scientific and clinical as well as private sector expertise, and members of the advocacy community. We have a very broad representation on that panel of the various issues that are going to affect or inform the research opportunities.

The Blue Ribbon Panel, as cited in the presidential memo, is charged with providing expert advice on what the scientific goals and opportunities are, and what barriers may exist, and how to bring down those barriers. Part of what the panel has been allowed to do is to assemble working groups that will focus on the specific areas that the Blue Ribbon Panel identified as having the potential to identify scientific opportunities that could be accelerated through the vice president’s cancer initiative.

The specific goals of the Blue Ribbon Panel are to:

• Identify those scientific opportunities and they’re not all scientific opportunities—they’re really the ones that are poised to be accelerated, where we have foundational knowledge that we can build on, but that we really need the support, emphasis and funding of this initiative to move it to the next level,

• Identify scientific and regulatory hurdles that can be overcome, the barriers that are preventing progress where we can identify them, and

• Suggest how to address the research gaps and how to move the science and the understanding of cancer forward.

We expect to only develop five to ten recommendations of opportunities that would be pursued. So the goals here is to focus in on a few opportunities and really invest in them, intellectually and monetarily to move them forward, and not to have this be business as usual where everything is funded.

As Doug said, NCI is going to continue to broadly support cancer research, but this is an opportunity to support a few opportunities that really are poised to be accelerated.

So what are the areas that the panel has identified? They fall into seven categories where it’s thought that there are specific areas that can be accelerated through this initiative:

• Cancer immunology and prevention,

• Tumor evolution and progression,

• Precision prevention and early detection,

• Expanding clinical trials,

• Pediatric cancer, which was pulled out as a separate working group because of the recognition that, in fact, pediatric cancer is distinct from adult cancer. Within the pediatric cancer working group, I think there will also be some discussion of adolescent and young adult cancer, which is yet another third category, and so that will be encompassed within pediatric cancer,

• Enhanced data sharing, and

• Implementation sciences.

The working groups have already been assembled. In fact, this week, all seven of them will have had their first meeting, and each working group is being asked to generate two to three recommendations that would then be forwarded to the Blue Ribbon Panel. The Blue Ribbon Panel is going to meet in the middle of June to review all of those recommendations, look for recommendations that are overlapping—we think there are a number of crosscutting issues that are going to emerge. They will then synthesize those recommendations into the five or ten that are going to be delivered to the NCAB, which will then deliver their recommendations to the NCI, which will go to the task force.

So crosscutting themes; I just alluded to the fact that we fully expect that there are going to be topics that come up in the working groups that are common, that really can be synergized:

• Prevention—that is going to appear in at least three or four of the working groups, and we think very strong recommendation can emerge from that topic,

• Technology and preclinical model development is, again, something that is going to filter through all of the working groups and is going to be a focus for much of them since those are areas that are quite limiting or barriers in progress in some of the areas,

• Data sharing and predictive computational modeling is another topic like technology and preclinical models that will filter through all of the working groups,

• Health disparities research,

• Tumor heterogeneity, and

• Biomarkers.

These are all topics that we expect will come up repeatedly and provide an opportunity for some comments and recommendations coming out of the Blue Ribbon Panel. The co-chairs of the working groups are members of the panel and the co-chairs the groups they are co-chairing are listed here. We have NCI staff who are also participating in the working groups, both as subject matter experts, but also to ultimately help formulate all the recommendations that are coming out. The goal really is to reduce the burden on the panel and the working groups, and you’ll see that the timeline demands that we try to ease the burden as much as possible.

I should point out that the Blue Ribbon Panel members were first announced on April 4, we had our first meeting April 1, and we had our second meeting one week later at April 18. Within those two meetings, the panel had already had sufficient discussions to identify and organize the working groups to volunteer to co-chair them and populate them.

The working groups are expected to have weekly meetings through May and probably the beginning of June with the goal of getting recommendations to the panel by the middle of June, where we will be discussing all of their recommendations and then going back iteratively with the working groups to refine them so that we have a final working report by August, which is when we have been charged with getting the report to the NCAB for its consideration.

I want to stop at this point and acknowledge my co-chairs on the panel—Elizabeth Jaffee [professor and deputy director for translational research at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University] and Tyler Jacks [chair of the National Cancer Advisory Board, and director of the Koch Institute for Integrative Cancer Research at MIT]—who have really done a phenomenal job in helping us really get this whole working group effort up and running. It’s really been a whirlwind, but I think we’re really making progress. The working group chairs have been phenomenal in adjusting their schedules, and giving a huge amount of thought to what are the opportunities, and I really expect that we’re going to have all aspirational recommendations coming out that are actually feasible to actually attain in a period of one to five years.

We also want to be sure that we get input from as broad a community as possible. This isn’t supposed to be the elite deciding what the opportunities are, it’s really supposed to be reaching out into not only the academic community, but the patient community and the broad community at large for ideas and recommendations.

Thanks to the Office of Communications here at NCI, there is an online public idea repository where everyone is encouraged to submit their ideas. We’re getting good ideas coming in from a broad sector—those are being downloaded every week—we’re going through them and forwarding them to the Blue Ribbon Panel and the working groups for consideration. There’s also an ability to submit ideas through email and through the phones.

We have been at AACR to let people know about the Cancer Research Ideas website, we’re also going to be at ASCO. There’s going to be a Blue Ribbon Panel listening session at ASCO on June 6, where members of the Blue Ribbon Panel are going to give some updates on what the panel has been doing, and answer questions, both to ASCO leadership and to any members who want to attend and contribute ideas.


DOROSHOW: I’m going to update you on the current and perhaps some of the future outputs of the Precision Medicine for Oncology initiative you all know about. As you know, as of December last year when President Obama signed the budget, we were the recipient of $70 million that actually came to the NCI by around February of last year. I think I have presented some of the goals for the use of that money that we talked about, that we negotiated, but just let me go through them one by one and tell you what we’ve done so far to use these new appropriated dollars:

• Goal one was to expand genomics-based clinical trials of targeted agents and immunotherapy,

• Goal two was to help us develop a better understanding of drug resistance, both through the use of combinations and also the immunotherapy as well as a targeted area,

• Three is to begin to try to improve our preclinical models that will be useful for drug resistance and also selecting therapy going forward, and

• About twenty percent of the funds have gone to help expand the Genomic Data Commons and to facilitate continuing development of our genomic data sharing activities.

Just to remind out, about the ongoing NCI MATCH trial, this trial will reopen after an incredible 800 patient accrual in three months. Last fall, it has been reanalyzed and expanded from 10 to 24 arms and we think that there will be very robust ongoing participation in this study.

What we’ve done to try to maximize with the information that we gained from that trial, using the precision medicine oncology funds, is to expand accrual to 5,000 patients, which should—based on the estimates from the first 800 patient sample and the tissue analysis of that sample—lead to a match rate of somewhere between 20 and 25 percent, with that assuming that type of match rate would also set aside funds so that not only will the initial panel of mutations be measured, but actually much more detailed. Molecular analyses for those patients who were actually on study will be performed, and that money is now assured.

Finally, in the area of clinical trials, now we’ve basically fully funded the Pediatric MATCH trial, which, in my understanding, is that good progress is being made toward the development of a final clinical protocol as well as negotiating with all of the companies necessary to expand the CRADAs that we have with those companies for pediatric use. The assumption is the actual match day will open, if not by the end of December, very early in January. The funding for that is now assured.

We’re also, as part of that first to aim for precision medicine, very interested in trying to expand our understanding of how immunotherapy works and doesn’t work. We had a workshop in January, the recommendations of which have been incorporated into two different administrative supplements—one went out in the middle of April, one just a few weeks ago to develop basically a consortium of institutions to try to help us take tissue from patients on immunotherapy trials and to understand the microenvironment and to develop assays that will put us in better standing in terms of understanding sensitivity and resistance.

We also issued a supplement request to try to specifically enhance our understanding of immunotherapy for pancreatic cancer and in particular, what obstacles around the pancreatic cancer microenvironment actually have to date made it difficult to utilize checkpoint inhibitors in that disease.

We really haven’t made a whole lot of progress; we think that we will by providing additional funds, specifically in these areas, to get additional tissues for very careful molecular analyses.

I’m in the difficult position of—since this is a public meeting—only asking you to stay tuned in suggesting that there might be areas that you will want to be attuned to in the future, and as soon as those things in the next several weeks become public, you will know about them, but they will affect this area that we continue and actually want to further expand and support.

The next thing I’m going to talk about very briefly is something that we’ve been working on starting last summer, and that is something we call the NCI Virtual Drug Formulary. I can tell you that, for years, I’ve heard and talked to many NCI-supported investigators—cancer center directors and others—bemoaning the fact that it’s difficult, if not impossible, in some circumstances to get drugs from two different companies to conduct precision medicine trials of combinations, because of the lengthy deliberations, negotiations, and other roadblocks that occur in that circumstance.

Frankly, given that amount of time that we all spend negotiating with companies, I’m very sympathetic to that issue. You probably don’t know that NCI has had, because of its negotiated relationships with many companies, the ability to do investigational combinations for about a decade, and we’ve actually accrued over the last five years something like 4,400 patients to investigational combinations. About 100 trials have been supported and yet, that’s nothing like the number that are potentially investigators around the country would like to conduct.

The reason that I was really about whether or not would we ever be able to do this is because of the time we had spent over many years trying to negotiate these issues with various companies.

But as it became clear that it would be possible to put together these 20-plus companies for the MATCH trial, the idea was rekindled, at least for me and several of my colleagues, that perhaps we should try again to develop a formulary, and not for a single trial, but for many trials that could be conducted at NCI-designated cancer centers. So we’ve been working very hard to try to do that.

We’ve met with many companies to date, and the idea is to create a system in which the NCI serves as the home for a virtual formulary of drugs that we would dispense, pay for the dispensing of, perform the auditing function, and utilize the central IRB for if necessary, to facilitate interactions between cancer center investigators and companies that provide their drugs for this formulary.

The idea would be that we would not only have investigational drugs, but also recently approved drugs that would be used for purposes for which they’re not FDA approved. These are some of the ideas that we’ve discussed with companies. We hope over 20 companies come in in less than a month to a big meeting at ASCO.

Stay tuned, I think this is really a way for us to facilitate investigator-initiated work in the area of combination investigational therapy to go on in the spirit of the Precision Medicine Initiative.

The third aspect of the goals for this project was to enhance our ability to tackle many areas of drug resistance. Of course, one is getting the combination agents, but the other is to do something that is really very difficult, and that is to utilize tissues from clinical trials to really understand why patients are sensitive or resistant as they go through treatments with a variety of different modes of therapy. Those goals, as was discussed with this group and others, really would be facilitated by the development of molecularly analyzed samples from patients with highly resistant tumors before, during, and after treatment, and also, an ability to really enhance the support for the groups that are facile around this area in the country.

I can’t say much further, but please stay closely tuned, because we are very interested in supporting this area of investigation with resources from the Precision Medicine Initiative.

What I can talk about are ways to try to improve preclinical models. Cancer center directors early in April received a request for supplements in the area of development of canine models of immunotherapy, naturally occurring tumors for the development of new antibodies and new approaches to analyze mutations in these tumors. I’d just remind you that there are more canine patients with non-Hodgkins lymphoma, many more than there are humans that develop non-Hodgkins lymphoma every year. It turns out that this was issued and we had, frankly, an overwhelming response from cancer centers and veterinary medical schools interested in participating. We’re very enthusiastic about the opportunities that this will give us to actually develop tissues, develop new approaches in spontaneously occurring tumors and then to test immunotherapies.

About just a week ago, we issued another supplement request—this is to really develop a preclinical models collaborative to develop new models and also to develop a much better way in a collaborative setting with multiple sites to test new agents that come into the NCI early phase therapeutics program, which has a very large number of CRADAs and a large number of agents to help us do a much better job of selecting what drugs to take in what diseases to clinical trials to do preclinical trials to develop better SOPs for those trials for the development of PDXs, and really to bring this very robust community that’s involved in developing these models.

The [Genomic Data Commons] that you’ve heard a lot about, I think, is really one of the most important if not the most important parts of the Precision Medicine Initiative for Oncology, because all the data that we’re going to generate, whether it’s through an immunology resource consortium, it’s got to be deposited somewhere and all of those data have to be available to the public. We need to work very closely for these initiatives and others with Dr. Warren Kibbe [NCI acting deputy director and director of the NCI Center for Biomedical Informatics and Information Technology] and others to make all of this information more widely available.

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