This program announcement must be read in conjunction with the General Application Instructions, version CD26_01.

Program Announcement for the Defense Health Agency

Breast Cancer Research Program Breakthrough Award Level 4

Funding Opportunity Number: HT942526BCRPBTA4

Pre-Application Due: June 12, 2026

Application Due: September 30, 2026 https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01

FY26 Breast Cancer Breakthrough Award Level 4 Award 2

Content

Before You Begin 3

Basic Information Summarizes the funding opportunity, funding details, submission deadlines and review dates

Eligibility Details eligibility factors for the applicant organization and Principal Investigator

Program Description Describes the program mission and intent of the Breakthrough Award Level 4;

provides key award information and considerations; and outlines funding details

Application Contents Presents the two-step application process and instructions for preparing a pre-application and full application

Submission Requirements Provides locations for application packages, instructions for submitting pre-applications and full applications, and describes application verification

Application Review Information Outlines the processes for application compliance review, pre-application and full application selection/notification, and risk assessment. Also, details the review criteria for pre-application screening and both tiers of the CDMRP application review process – Peer Review and Programmatic Review

Federal Award Notices Outlines what a successful applicant can expect if recommended for funding

Post-Award Requirements References policy requirements for funded research; outlines reporting requirements and restrictions related to Principal Investigator changes and institutional award transfers

Other Information Outlines criteria for administrative actions including application rejection, modification, withdrawal and withhold

Appendix 1 Includes a checklist for all full application components to facilitate application submission

Appendix 2 Acronym List

FY26 Breast Cancer Breakthrough Award Level 4 Award 3

Before You Begin

• Active SAM.gov, eBRAP.org and Grants.gov registrations are required for application submission. User registration for each of these websites can take several weeks or longer.

Each applicant must ensure their registrations are active and up to date prior to application preparation.

• Read this funding opportunity announcement in the order it is written before beginning to prepare application materials. It is the responsibility of the applicant to determine whether the proposed research meets the intent of this funding opportunity and that all parties meet eligibility requirements.

• To support application preparation, additional resources are available including an application process FAQ, a Guide for Intragovernmental & Intramural Applicants and a CDMRP Video Series detailing the application process.

Who to Contact for Support

This document uses internal links; you can go back to where you were by pressing the Alt + left arrow keys (Windows) or command + left arrow keys (Macintosh) on your keyboard.

Click to be taken to additional guidance and instructions within the General Application Instructions (GAI).

eBRAP Help Desk

301-682-5507 help@eBRAP.org

Questions regarding funding opportunity submission requirements, as well as technical assistance related to pre-application or intramural application submission.

Grants.gov Support Center

800-518-4726 International: 1-606-545-5035 support@grants.gov

Questions regarding Grants.gov registration and Workspace.

https://sam.gov/ https://ebrap.org/eBRAP/public/index.htm https://grants.gov/register https://cdmrp.health.mil/#:%7E:text=Frequently%20Asked%20Questions%20%C2%BB https://cdmrp.health.mil/#:%7E:text=Guide%20for%20Intragovernmental%20%26%20Intramural%20Applicants https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Journey%20of%20an,Tier%20Review%20Process mailto:help@eBRAP.org mailto:support@grants.gov https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01

Section Shortcuts Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 4

1. Basic Information About the Funding Opportunity

Summary: The fiscal year 2026 (FY26) Breast Cancer Research Program (BCRP) Breakthrough Award mechanism supports promising research with high potential to lead to or make breakthroughs in breast cancer. All applications must address at least one of the FY26 BCRP overarching challenges or provide adequate justification for exception. Applications must address the challenge in a way that can lead to a breakthrough and have major impact. The FY26 Breakthrough Award mechanism contains four different funding levels designed to support major (but not all) stages of research that will lead to clinical application. Each level specifies a distinct research scope. This program announcement discusses the Breakthrough Award Level 4.

Distinctive Features:

• Clinical trials are required.

• The research team must include two or more breast cancer consumer advocates.

• This funding mechanism allows for a single Principal Investigator (PI), or two partnering PIs referred to as the Initiating PI and the Partnering PI. For the Partnering PI Option (PPIO), only the Initiating PI will submit a pre-application, but both PIs will need to submit at the full application stage. Be advised, failure to submit all associated (Initiating and Partnering PI) applications by the deadline may result in administrative withdrawal.

Funding Details: The Congressionally Directed Medical Research Programs (CDMRP) expects to allot roughly $21 million (M) to fund approximately one Breakthrough Award Level 4 application with a total cost cap of $21M. The maximum period of performance is four years. It is anticipated that the award made from this FY26 funding opportunity will be funded with FY26 funds, which will expire for use on September 30, 2032. The award supported with FY26 funds will be made no later than September 30, 2027.

Submission and Review Dates and Times

• Pre-Application (Preproposal) Submission Deadline: 5:00 p.m. Eastern Time (ET), June 12, 2026

• Invitation to Submit an Application: July 16, 2026

• Application Submission Deadline: 11:59 p.m. ET, September 30, 2026

• End of Application Verification Period: 5:00 p.m. ET, October 5, 2026

• Peer Review: December 2026

• Programmatic Review: January 2027

• Invitation for Oral Presentation: February 2027

• Programmatic Review, Stage 2: March 2027 Announcement Type: Initial Funding Opportunity Number: HT942526BCRPBTA4 Assistance Listing Number: 12.420

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 5

2. Eligibility Information

2.1. Eligible Applicants

2.1.1. Organization

Extramural and intramural U.S. Department of War (DOW) organizations are eligible to apply, including foreign and domestic organizations, for-profit and nonprofit organizations, and public or private entities.

2.1.2. Principal Investigator

Independent investigators affiliated with an eligible organization are eligible to be named as PI, Initiating PI, or Partnering PI on the application, regardless of ethnicity, nationality or citizenship status.

There are no limits on the number of pre-applications an investigator may submit as a PI, Initiating PI, or Partnering PI for this Breakthrough Award Level 4 program announcement.

This program announcement discourages investigators from being named on multiple pre-applications unless they are clearly addressing distinct research questions. Invited applications must include a brief description of all the applications in which the investigator is named as a PI, Initiating PI, Partnering PI, or collaborator under this Breakthrough Award Level 4 program announcement.

2.2. Cost Sharing

Cost sharing is not an eligibility requirement.

2.3. Other

Awards are made to eligible organizations, not to individuals. Refer to the GAI for additional recipient qualification requirements.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Content_Form_Full_App_Submission:%7E:text=pre%2Dapplication%20submission.-,Extramural%20Organization%3A,-A%20foreign%20or https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:%7E:text=Intramural%20DOW%20Organization%3A%20A%20subset%20of%20intragovernmental%20organizations%3B%20refers%20specifically%20to%20DOW%20organizations%2C%20including%20DOW%20laboratories%2C%20DOW%20military%20treatment%20facilities%2C%20and/or%20DOW%20activities%20embedded%20within%20a%20civilian%20medical%20center https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=APPENDIX%201-,RECIPIENT%20QUALIFICATION%20AND%20RESTRICTION%20INFORMATION,-A.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 6

3. Program Description

The Defense Health Agency Contracting Activity (DHACA) is soliciting applications to this funding opportunity using delegated authority provided by United States Code, Title 10, Section 4001 (10 USC 4001). The CDMRP is the program office managing this FY26 funding opportunity as part of the BCRP. The CDMRP is located within the Defense Health Agency Research and Development (DHA R&D), which is a part of the Department of Defense, DOD, herein referred to using the secondary title Department of War, DOW. Congress initiated the BCRP in FY92 to support innovative, high-impact research, with a mission of ending breast cancer for Service Members and their Families, Veterans, and the general public. Appropriations for the BCRP from FY92 through FY25 totaled $4.52 billion. The FY26 appropriation is $145M.

The BCRP challenges the scientific community to design research that will address the urgency of ending breast cancer. Specifically, the BCRP seeks to accelerate high-impact research with clinical relevance, encourage innovation and stimulate creativity, and facilitate productive collaborations.

The BCRP brief overview, called The Breast Cancer Landscape, describes what is currently known about the most pertinent topics that are consistent with the BCRP’s mission of ending breast cancer. Considering the current breast cancer landscape and the program’s mission, the BCRP seeks to invest in research that addresses the following FY26 BCRP overarching challenges:

• Prevent breast cancer (primary prevention)

• Identify determinants of breast cancer initiation, risk, or susceptibility

• Distinguish deadly from non-deadly breast cancers

• Conquer the problems of overdiagnosis and overtreatment

• Identify what drives breast cancer growth; determine how to stop it

• Identify why some breast cancers become metastatic

• Determine why/how breast cancer cells lie dormant for years and then re-emerge; determine how to prevent lethal recurrence

• Revolutionize treatment regimens by replacing them with ones that do all of the following:

improve survival, are more effective, and are less toxic

• Eliminate the mortality associated with metastatic breast cancer

3.1. Intent of the Breakthrough Award Level 4

The intent of the FY26 BCRP Breakthrough Award is to support promising research with high potential to lead to or make breakthroughs in breast cancer.

The FY26 BCRP Breakthrough Award contains four different funding levels, each intended to support a defined research scope. It is the responsibility of the PI to select the level that aligns with the scope of the proposed research. The PI should select the funding level based on the research scope defined in the program announcement, and not on the amount of the budget.

The BCRP will not recommend for funding an application that does not meet the intent of the funding level selected, even if it might meet the intent of a different funding level.

https://cdmrp.health.mil/bcrp/pdfs/BreastCancerLandscape2025.pdf

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 7

This program announcement discusses the FY26 BCRP Breakthrough Award Level 4

(BTA4).

Funding Level 4: This funding level supports large-scale projects, including comparative effectiveness trials, that will transform and revolutionize the clinical management of and/or the prevention of breast cancer. This funding level requires clinical trials. PIs should have experience in successfully leading large-scale projects and demonstrated ability (through personal experience or via a commitment from a collaborating clinical investigator) to implement a clinical trial successfully. Where relevant, the application must demonstrate proof of the availability of, and access to, necessary data, samples, cohort(s) and/or critical reagents for the proposed research. If the project requires U.S. Food and Drug Administration (FDA) or an equivalent international regulatory agency involvement, the application must include the following readiness requirements: proof of the availability of, and access to, clinical reagents that meet regulatory compliance guidelines; proof of the availability of, and access to, appropriate subject population(s); validated projections for patient recruitment; and proof of submission of an Investigational New Drug (IND), Investigational Device Exemption (IDE), or equivalent to the relevant regulatory agency.

3.1.1. Key Elements for the BTA4

Impact: Proposed research must have the potential for a major impact and accelerate progress toward ending breast cancer. The near-term and/or long-term impact must move beyond a minor advancement and have the potential to lead to a fundamentally new strategy or approach to preventing or ending breast cancer that is significantly more effective than current strategies or approaches. Applications must identify the breast cancer patients or at-risk individuals who would ultimately benefit from the proposed research.

Overarching Challenges: Considering the current breast cancer landscape and the BCRP’s mission, all applications must address at least one of the above overarching challenges unless adequate justification for exception is provided.1 Simply identifying an overarching challenge is not sufficient. Applications must address the challenge in a way that can lead to or make a breakthrough and have a major impact. The BCRP strongly urges applicants to read and consider The Breast Cancer Landscape before preparing their applications.

Personnel: Applications must include an appropriate and robust research team with the combined backgrounds and breast cancer-related expertise to enable successful conduct of the project.

Consumer Advocates: Applications must include two or more breast cancer consumer advocates as integral members of the research team throughout the planning and implementation of the research project. The investigator(s) should involve consumer advocates in the development of the research question, project design, oversight, and evaluation, as well as other significant aspects of the proposed project. Team members must maintain well-integrated and ongoing interactions with consumer advocates that extend beyond attending seminars and semi-annual meetings. As lay representatives, the consumer advocates must be individuals who have been diagnosed with breast cancer and are actively involved in a breast cancer advocacy organization. They must perform their role independently of their employment and cannot be employees of any organization participating in the application. The consumer advocates should have a high level of knowledge of current breast cancer issues and the

1 With adequate justification, applications may identify and address another overarching challenge related to The Breast Cancer Landscape. Investigators must provide justification in the application.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#:%7E:text=Clinical%20Trial%3A,health%2Drelated%20outcomes.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#:%7E:text=Clinical%20Trial%3A,health%2Drelated%20outcomes.

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 8 appropriate background and/or training in breast cancer research to contribute to the project.

The consumer role should focus on providing objective input throughout the research effort and its potential impact for individuals with, or at risk for, breast cancer.

Partnering PI Option: The BTA4 PPIO encourages applications that include meaningful and productive partnerships between two PIs. One PI will be identified as the Initiating PI and will be responsible for the majority of the administrative tasks associated with application submission.

The other PI will be the Partnering PI. Both PIs should contribute significantly to the development and execution of the proposed research project. The PIs may have expertise in similar or disparate scientific disciplines, but each PI must bring distinct contributions to the application. The application should clearly demonstrate that both PIs have equal intellectual input into the design of the project and will devote similar levels of effort to the conduct of the project. The application should balance funding between both PIs unless appropriately justified.

The PPIO encourages, but does not require, new partnerships. The application should describe how the PIs’ unique expertise combined as a partnership will better address the research question, how the unique expertise that each individual brings to the application is critical for the research strategy and completion of the proposed project, and why the work should be done together rather than through separate efforts. To meet the intent of the PPIO, the BCRP discourages applicants from being named as a Partnering PI on multiple BTA4 applications unless they are clearly unique, meaningful partnerships addressing distinct research questions. Applications where one PI is providing samples, animal models, or investigational agents, while the other PI is conducting most or all of the experiments and analyses, do not meet the intent of the PPIO. If recommended for funding, each PI will be named on separate awards to the recipient organization(s). Each award will be subject to separate reporting, regulatory, and administrative requirements. For individual submission requirements for the Initiating and Partnering PIs, refer to Section 5.3, Submission Instructions.

In addition to items outlined above, when developing applications to the FY26 BCRP BTA4 mechanism, the BCRP strongly encourages applicants to provide sufficient evidence to demonstrate the following key considerations:

• Sufficient access to and availability of the study population.

• Adequate access to and availability of the intervention.

• Appropriate statistical considerations, data management and analysis plans appropriate for the proposed research.

3.1.2. Other Important Considerations for the BTA4

The FY26 BCRP BTA4 application review requires an invited oral presentation, as described in Section 4.4.

In accordance with the National Defense Authorization Act for Fiscal Year 2026, Section 732, CDMRP does not support the conduct of painful research (U.S. Department of Agriculture pain category D or E) involving domestic cats or dogs, except for studies relating to military or service animals.

Funding from this award mechanism must support a clinical trial.

Applicants seeking funding for research that does not meet the definition of a clinical trial should consider other FY26 BCRP funding opportunities that may be more appropriate for such research.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:%7E:text=or%20hardware%20procurement.-,Clinical%20Trial%3A,-As%20defined%20in

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 9

An informational resource for preparing an application, the Human Subject Research Resource, is available on the CDMRP website.

The proposed clinical trial is expected to begin no later than 12 months after the award date or 18 months after the award date for studies regulated by the Regulatory Agency. Unless otherwise noted, for the purposes of this funding opportunity, Regulatory Agency refers to the FDA or any equivalent international regulatory agency.

All projects should adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of clinical and preclinical research, such as those described in the STROBE, CONSORT, SPIRIT and ARRIVE 2.0 guidelines.

The proposed research must be relevant to Service Members, Veterans, their Families, and/or the American Public. PIs are encouraged to integrate and/or align their research projects with DOW and/or VA research laboratories and programs. Collaboration with the DOW and/or VA is also encouraged. A list of websites that may be useful in identifying additional information about ongoing DOW and VA areas of research interest or potential opportunities for collaboration can be found in Appendix 10 of the GAI.

A congressionally mandated Metastatic Cancer Task Force was formed with the purpose of identifying ways to help accelerate clinical and translational research aimed at extending the lives of advanced state and recurrent patients. As a member of the Metastatic Cancer Task Force, the CDMRP encourages applicants to review the task force recommendations and submit research ideas to address these recommendations provided they are within the limitations of this funding opportunity and align with the FY26 BCRP priorities.

3.2. Funding Instrument

The funding instrument for awards made under the program announcement will be cooperative agreements (31 USC 6305) based on anticipated “substantial involvement” on the part of CDMRP. Substantial involvement means that, after award, CDMRP staff will assist, guide, coordinate, and/or participate in project activities, including but not limited to, Milestone Meetings, wherein recommendations for continued funding will be made based on overall study progress.

3.3. Funding Details

Period of Performance: The maximum period of performance is four years.

Cost Cap: For applications with a single PI, the application’s total costs budgeted for the entire period of performance should not exceed $21M. For Partnering PI Option applications, the combined total costs budgeted for the entire period of performance in the applications of the Initiating PI and the Partnering PI should not exceed $21M. If indirect cost rates have been negotiated, indirect costs are to be budgeted in accordance with the organization’s negotiated rate. Collaborating organizations should budget associated indirect costs in accordance with each organization’s negotiated rate.

All direct and indirect costs of any subaward or contract must be included in the direct costs of the primary award.

The applicant may request the entire maximum funding amount for a project that may have a period of performance less than the maximum four years.

The appropriateness of the budget for the proposed research will be assessed during peer review.

https://cdmrp.health.mil/#:%7E:text=Human%20Subject%20Research%20Resource https://www.strobe-statement.org/ https://www.nature.com/articles/s41591-025-03635-5#:%7E:text=SPIRIT%20and%20CONSORT%20are%20evidence,relevant%20empirical%20evidence%20where%20possible https://www.nature.com/articles/s41591-025-03668-w?fromPaywallRec=false https://arriveguidelines.org/arrive-guidelines https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#DOW_AND_VA_WEBSITES https://health.mil/Reference-Center/Congressional-Testimonies/2018/05/03/Metastatic-Cancer-Research https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=Period%20of%20Performance%3A%20The%20time%20interval%20between%20the%20start%20of%20a%20federal%20award%20and%20the%20planned%20end%20date.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=in%20project%20activities.-,Cost%20Cap%3A,-The%20maximum%20cost

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 10

For Partnering PI Option Applications: A separate award will be made to each PI’s organization.

Direct Cost Restrictions: For this award mechanism, direct costs:

Must be requested for:

• Costs associated with meetings described in Section 8.3.

May be requested for (not all-inclusive):

• Travel in support of multi-institutional collaborations.

• Costs for three investigator(s) to travel to one scientific/technical meeting per year in addition to the required meeting described in Section 8.3. The intent of travel to scientific/technical meetings should be to present project information or disseminate project results from the FY26 BCRP Breakthrough Award Level 4.

• Research subject compensation and reimbursement for trial-related out-of-pocket costs (e.g., travel, lodging, parking, costs associated with caregiving, and resources/equipment to enable participation).

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 11

4. Application Contents and Format

4.1. Application Overview

Application submission is a two-step process requiring both a pre-application submitted via the Electronic Biomedical Research Application Portal (eBRAP) and a full application submitted through eBRAP or Grants.gov. Depending on the submission portal, certain aspects of the application will differ.

Intramural DOW organizations submitting a full application should follow instructions for submission through eBRAP.

Extramural organizations submitting a full application must follow instructions for submission through Grants.gov.

4.2. Pre-Application Components

The initiating PI must submit the following pre-application components.

Upload documents as individual PDF files unless otherwise noted. Files must comply with the formatting guidelines listed in the GAI.

• Preproposal Narrative: Provide responses in the appropriate data fields for the following:

○ Which BCRP overarching challenge(s) will the proposed research address? If “other,” state the overarching challenge and provide justification within the context of the breast cancer landscape. Simply identifying an overarching challenge is not sufficient. (200-character limit)

○ How will the proposed research lead to a major impact for the overarching challenge(s)?

Explain how the research meets the requirement for high potential to lead to or make a breakthrough and accelerate progress toward ending breast cancer. (2,000-character limit)

○ How will the proposed research move beyond a minor advancement? How will the research lead to a fundamentally new strategy or approach to preventing or ending breast cancer that is significantly more effective than current strategies or approaches?

(2,000-character limit)

○ Briefly state how the scope of the proposed research is appropriate for Funding Level 4 as described in this program announcement. (500-character limit)

○ Project Readiness: State the clinical intervention, subject population(s), and phase of the clinical trial proposed. Describe a plan for project readiness by the full application deadline with respect to the availability of, and access to, clinical reagents (e.g., therapeutics) that meet regulatory compliance guidelines; the availability of, and access to, appropriate subject population(s); and submission of an IND, IDE, or equivalent to the Regulatory Agency by the FY26 BCRP Breakthrough Award Level 4 application submission deadline, if applicable. (3,000-character limit) https://ebrap.org/eBRAP/public/index.htm https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=APPENDIX%202.%0AFORMATTING%20GUIDELINES https://cdmrp.health.mil/bcrp/pdfs/BreastCancerLandscape2025.pdf https://cdmrp.health.mil/bcrp/pdfs/BreastCancerLandscape2025.pdf https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Full_App_Submission_Grants:%7E:text=IV.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20FULL%20APPLICATION%20SUBMISSION%20THROUGH%20GRANTS.GOV https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Full_App_Submission_eBRAP:%7E:text=V.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20FULL%20APPLICATION%20SUBMISSION%20THROUGH%20eBRAP

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 12

• Pre-Application Supporting Documentation: The items to be included as supporting documentation for the pre-application must be uploaded as individual files and are limited to the following:

○ One page for additional information that the PI can use, at their discretion, to provide supporting data or rationale for the pre-application.

○ If applicable, one page to provide a list of all FY26 BCRP Breakthrough Award Level 4 pre-applications in which the investigator is named as a PI, Initiating PI, Partnering PI or collaborator. Include the CDMRP log number, role on the project, project title, specific aims, and a brief description of how each pre-application will address distinct research questions.

4.3. Full Application Components

Applicants must receive an invitation to submit a full application. Uninvited full application submissions will be rejected.

Partnering PI Option: The CDMRP requires separate full application package submissions for the Initiating PI and each Partnering PI, even if the PIs are located within the same organization.

The application submission process for the Partnering PI uses an abbreviated full application package.

4.3.1. Full Application Components for the PI or Initiating PI

Each application submission must include the completed full application package for this program announcement. See Appendix 1 for a checklist of the full application components.

(a) SF424 Research & Related Application for Federal Assistance Form (Grants.gov submissions only):

IMPORTANT: When completing the SF424 R&R, enter the eBRAP log number assigned during pre-application submission into Block 4a – Federal Identifier.

(b) Attachments:

Each attachment of the full application components must be uploaded as an individual file in the format specified and in accordance with the formatting guidelines in the GAI.

○ Attachment 1: Project Narrative (20-page limit): Upload as

“ProjectNarrative.pdf”.

Describe the proposed project in detail using the outline below. It should be evident that the proposed study meets the definition of a clinical trial.

– Background: Describe in detail the scientific rationale for the study. Provide a review and analysis of the available literature and completed/ongoing studies relevant to the proposed clinical trial.

Describe the preliminary studies and/or preclinical data that support the proposed clinical trial. Importantly, describe the studies showing proof of concept and efficacy in in vivo system(s) that led to the current proposed clinical trial.

Summarize key preclinical pharmacological findings, dosage studies and other clinical studies (if applicable) that examine the safety and stability (as appropriate) of the intervention.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=APPENDIX%202.%0AFORMATTING%20GUIDELINES https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=Clinical%20Trial%3A,health%2Drelated%20outcomes.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=(a)%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20SF424%20(R%26R)%20%E2%80%93%20Application%20for%20Federal%20Assistance%20Form https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Project%20Narrative%3A,-Attach%20as%20%E2%80%9CProjectNarrative

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 13

Provide a summary of other relevant ongoing, planned or completed clinical trials, and describe how the proposed study differs.

For proposed clinical trials initiated using other funding prior to this application, explain the history and background of the clinical trial and declare the source(s) of prior funding. Identify the specific portions of the study that funding from this award would support.

– Intervention: Identify the intervention to be tested. Include the following components, as applicable: intervention type (drug, device, surgical, etc.), complete name and composition, source, general concept of design, and administration route.

Indicate who holds the intellectual property rights to the intervention, if applicable, and how the PI has obtained access to those rights, along with access to the intervention itself, for conduct of the clinical trial. As applicable, appropriate letters of commitment should be provided in Attachment 2: Supporting Documentation, demonstrating the study team’s access to the intervention(s) for the duration of the clinical trial. Describe how the intervention addresses current clinical needs and how it compares with currently available interventions and/or standards of care.

– Objectives, Specific Aims and Hypotheses: Describe the purpose of the proposed study with detailed objectives. State the hypothesis/research question to be tested in the proposed clinical trial and detail the specific aims that will address the hypothesis/research question.

– Study Design: Describe the proposed clinical trial in sufficient detail to evaluate its appropriateness and feasibility, relating to both the scientific success of the study and setting reasonable expectations of what study participants will experience.

Consult appropriate guidelines to ensure relevant aspects of rigorous and reproducible research are adequately planned for and, ultimately, reported.

Describe the type of study to be performed. Outline the proposed clinical trial methodology and study variables in sufficient detail to demonstrate a clear course of action and justification. Describe the interaction with the human subject, including the study intervention that they will experience, and include the dose and administration route. Provide sufficient detail in chronological order for a person not involved in the study to understand what the study participant will experience.

Provide a schedule (e.g., flowchart or diagram) of study intervention(s), evaluation(s), and follow-up procedures, including, if applicable, the biospecimen that will be collected, the collection schedule and amount. Describe measures to ensure consistency of dosing. Define each arm/study group of the proposed trial, if applicable, and describe how group assignment will occur. Include a description of controls, as appropriate. Specify the approximate number of study participants to be enrolled. Indicate whether subjects, clinicians, data analysts and/or others will be blinded during the study. Describe any other measures to be taken to reduce bias.

Define all endpoints/outcome measures relevant to the objectives of the study;

explain why they were chosen, and describe how, when and where they will be measured. Include all evaluations that will be made for study purposes. If questionnaires or other research data collection instruments will be used, include a copy of them in Attachment 2: Supporting Documentation. Describe the reliability and validity of the selected endpoints/outcome measures and

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 14 evaluations, along with the applicable quality standards. Explain how the results of evaluations and/or data collection instruments will be used to meet the objectives of the study (or to monitor safety of human subjects).

Briefly describe the study population and the inclusion and exclusion criteria that will be used to meet the needs of the proposed clinical trial. Additional details should be provided in Attachment 6: Study Population Recruitment and Safety Plan.

– Statistical Plan and Data Analysis: Describe the statistical model and data analysis plan with respect to the study objectives. Ensure sufficient information is provided to allow for a thorough evaluation of statistical calculations during review of the application.

Include a complete power analysis to demonstrate that the proposed clinical trial’s anticipated sample size is appropriate to meet the objectives of the study.

Describe all clinical and statistical justifications and assumptions that support the sample size calculations. Explain any anticipated subgroup analyses and demonstrate that such analyses will be appropriately powered.

Describe the strategy for how sex will be considered as a biological variable. This strategy should include a brief discussion of what is currently known regarding sex differences in the applicable research area. Clearly articulate how sex as a biological variable will be factored into the data analysis plan and how data will be collected and disaggregated by sex. Refer to the CDMRP Directive on Sex as a Biological Variable in Research for additional information.

For phase 3 clinical trials, describe plans for the valid and sufficiently powered analysis of group differences on the basis on sex, race and/or ethnicity as appropriate for the scientific goals of the study. Refer to the CDMRP Directive on the Inclusion of Women and Minorities as Subjects in Clinical Research for additional information on the requirements for phase 3 studies.

– Pitfalls and Mitigation Strategy: Describe potential challenges and discuss alternative methods/approaches that may be employed to overcome them.

○ Attachment 2: Supporting Documentation: Combine and upload as a single file named “Support.pdf”.

There are no page limits for these components unless otherwise noted. Include only components described below; inclusion of items not requested or viewed as an extension of the Project Narrative will result in the removal of those items or may result in administrative withdrawal of the application.

References Cited: List the references cited in the Project Narrative using a standard reference format (include URLs, if available).

List of Abbreviations, Acronyms and Symbols: Provide a list of abbreviations, acronyms and symbols.

Facilities, Existing Equipment and Other Resources: Describe the facilities and equipment available for performance of the proposed project; include any additional facilities or equipment proposed for acquisition at no cost to the award. Indicate whether government-furnished facilities or equipment are proposed for use. If so, reference the original or present government award under which the facilities or https://cdmrp.health.mil/pubs/pdf/CDMRP%20SABV%20Directive_Revised_MAR2025_signed.pdf https://cdmrp.health.mil/pubs/pdf/CDMRP%20SABV%20Directive_Revised_MAR2025_signed.pdf https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Directive%20on%20Inclusion%20of%20Women%20and%20Minorities%20as%20Subjects%20in%20Clinical%20Research https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Directive%20on%20Inclusion%20of%20Women%20and%20Minorities%20as%20Subjects%20in%20Clinical%20Research https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Supporting%20Documentation%3A,-Combine%20and%20attach

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 15 equipment items are now accountable. There is not a standardized form for this information.

Publications and/or Patents: Include a list of relevant publication URLs and/or patent abstracts. If articles are not publicly available, then copies of up to five published manuscripts may be included in Attachment 2. Extra items will not be reviewed.

Letters of Support: Provide individual letters signed by collaborating individuals and/or organizational officials demonstrating that the PI has the support and resources necessary for the proposed work for the duration of the proposed clinical trial. Letters from the PI’s Department Chair, or appropriate organization official, should also confirm that the PI(s) meet eligibility criteria. If applicable, provide a letter of support, signed by the lowest-ranking person with approval authority, confirming participation of intramural DOW collaborator(s) and/or access to military populations, databases or DOW resources. If applicable, provide a letter of support signed by the VA Facility Director(s), or an individual designated by the VA Facility Director(s), confirming access to VA patients, resources and/or VA research space.

Consumer Advocate Letters of Commitment: Provide a letter signed by each consumer advocate confirming their commitment to participate in the proposed project.

Research Sharing Plan: Describe the type of data or research resources to be made publicly available as a result of the proposed work. Describe the mechanism (e.g., direct sharing, repository, mixed mode) by which data and resources generated during the period of performance will be shared with the research community and other affected communities, including clinical trial participants. If applicable, include the name of the repository(ies) where scientific data and resources arising from the proposed clinical trial will be archived. Identify and provide the rationale for any data or resources that will not be shared (e.g., for intellectual property, feasibility, cost, or other considerations). The plan should also protect participant privacy, confidential and proprietary data, and performer/third-party intellectual property. Provide a milestone plan for disseminating data/results including when data and resources will be made available to other users. In cases where the study participant could potentially derive medical or other benefit from the information, explain whether the results of screening and/or study participation will be shared with the participant or their primary care provider, including results from any screening or diagnostic tests performed as part of the study.

Do not submit a copy of the National Institutes of Health (NIH) Data Management and Sharing Plan or duplicate the Data Management Plan, which will be requested only after a recommendation for funding is made.

Refer to the CDMRP Directive on Sharing Data and Research Resources for more information about the CDMRP’s expectations for making data and research resources publicly available.

Questionnaires and Other Research Data Collection Instruments: Include a copy of the most recent version of questionnaires, data collection forms, rating scales, interview guides or other instruments. This should include any drafts that are currently in use or underdevelopment.

https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Directive%20on%20Sharing%20Data%20and%20Research%20Resources

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 16

○ Attachment 3: Technical Abstract (one-page limit): Upload as “TechAbs.pdf”.

Write the technical abstract using the outline below. Clarity and completeness within the space limits are highly important.

– Background: Present the ideas and rationale behind the proposed clinical trial.

– Overarching Challenge(s): State the overarching challenge(s) that the proposed research will test, and briefly state how the project will address the challenge in a way that can lead to or make a breakthrough and have a major impact. Simply identifying an overarching challenge is not sufficient.

– Hypothesis/Objective(s): State the objective(s) of the proposed clinical trial and the hypothesis/research question to be addressed.

– Specific Aims: State the specific aims of the study.

– Study Design: Briefly describe the study design, including appropriate controls.

– Impact: Briefly describe how the proposed project will lead to a major impact for the overarching challenge(s). Explain how the research meets the requirement for high potential to lead to or make a breakthrough and accelerate progress toward ending breast cancer

– Military Relevance: Describe how the study is relevant to military health.

○ Attachment 4: Lay Abstract (one-page limit): Upload as “LayAbs.pdf”.

The lay abstract should address the points outlined below in a manner that is readily understood by readers without a background in science or medicine. Avoid overuse of scientific jargon, acronyms and abbreviations. Do not duplicate the technical abstract.

– Clearly describe the scientific rationale, objective and aims of the application.

– Describe the ultimate applicability of the research.

Which overarching challenge(s) does this research address?

What types of patients or at-risk individuals will it help and how will it help them?

What are the potential clinical applications, benefits and risks?

What is the projected timeline for achieving a patient-related outcome?

How will the proposed project lead to or make a breakthrough in breast cancer and accelerate progress toward the BCRP’s mission of ending breast cancer?

How is the proposed research relevant to Service Members, Veterans and their

Families?

○ Attachment 5: Statement of Work (six-page limit): Upload as “SOW.pdf”.

Refer to eBRAP for the Suggested SOW Format.

For guidance on preparing the SOW, refer to the Example: Assembling a Clinical Research and/or Clinical Trial Statement of Work. Include milestones for data or research resource(s) sharing.

Partnering PI Option: Each PI must submit an identical copy of a jointly created SOW. The specific contributions of the Initiating PI and the Partnering PI should be clearly noted for each task.

https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Suggested%20SOW%20Format https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Example%3A%20Assembling%20a%20Clinical%20Research%20and/or%20Clinical%20Trial%20Statement%20of%20Work https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Example%3A%20Assembling%20a%20Clinical%20Research%20and/or%20Clinical%20Trial%20Statement%20of%20Work https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Technical%20Abstract%3A,-Attach%20as%20%E2%80%9CTechAbs https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Lay%20Abstract%3A,-Attach%20as%20%E2%80%9CLayAbs https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Statement%20of%20Work%3A,-Attach%20as%20%E2%80%9CSOW

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Breast Cancer Breakthrough Award Level 4 Award 17

○ Attachment 6: Study Population Recruitment and Safety Plan (no page limit):

Upload as “StudyPopPlan.pdf”. Include the components listed below.

Enrollment Distribution: Provide anticipated enrollment table(s) with the proposed enrollment distributed on the basis of sex, race and ethnicity using the Public Health Service (PHS) Inclusion Enrollment Report. The enrollment table(s) should be appropriate to the objectives of the study.

Inclusion/Exclusion Criteria: List the inclusion and exclusion criteria for the proposed clinical trial. If limiting inclusion by age, race, ethnicity or sex, provide strong rationale based on justification from scientific literature, preliminary data or other relevant considerations. List and describe any evaluations (e.g., laboratory procedures, history or physical examination) that are required to determine eligibility/suitability for study participation and the diagnostic criteria for entry.

Describe how the study population represents the population anticipated to benefit from the intervention.

Study Population Availability: Demonstrate that the research team…