Key Dates

Related Announcements

Related Announcements

PAR-20-313 - Assay Validation of High Quality Markers for Clinical Studies in Cancer (UH2/UH3 Clinical Trial Not Allowed)

PAR-20-314 - Assay Validation of High Quality Markers for Clinical Studies in Cancer (UH3 Clinical Trials Not Allowed)

PA-22-176 - PHS 2021-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)

PA-22-178 - Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)

PAR-21-330 - Utilizing the PLCO Biospecimens Resource to Bridge Gaps in Cancer Etiology and Early Detection Research (U01 Clinical Trial Not Allowed)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PAR-22-216 - NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional)

Issued by

National Cancer Institute (NCI)

Purpose

Purpose

The purpose of this Notice of Special Interest (NOSI) is to encourage research studies leveraging partnerships between biomarker technology developers with assays for early cancer detection, and population-based researchers, including cohort and biorepository researchers. Proposals that facilitate early cancer biomarker assay development, verification, qualification, and validation utilizing statistically powered retrospective cohorts and/or through prospective studies in the appropriate populations with a sound study design are responsive to this NOSI.

Background

Established screening recommendations for the average risk population exist only for a few common cancers in the United States (e.g., breast, colorectal, cervix). Detecting cancers earlier may improve patient outcomes and reduce cancer-related mortality. However, most malignancies lack recommended screening programs. Together, cancers without screening programs account for a majority of new cancer cases and cancer related deaths and tend to be diagnosed at advanced stages with a worse prognosis. Moreover, even for those cancers with screening recommendations, the uptake of screening is not optimal, especially in underserved populations. As a result, there has been much interest in developing non-invasive screening biomarkers that can be measured in a blood sample or other easily obtained biospecimen (e.g., sputum or urine).

Liquid biopsy is being explored as a potential method to facilitate the early detection of cancer. Liquid biopsy generally refers to detecting circulating tumor cells (CTC), circulating tumor DNA (ctDNA), circulating extracellular vesicles and particles (EVPs) and other analytes in body fluids, such as serum, plasma, urine. Levels of ctDNA and different ctDNA biomarkers have been associated with more advanced disease and worse prognosis. In addition, some liquid biopsy technologies may be used to help guide selection of targeted therapies. Since the levels of these biomarkers tend to be lower in individuals at early cancer stages or prior to cancer symptoms, examining the use of these markers for early detection has been challenging. Newer technologies have improved limits of detection and the ability to detect multiple analytes from the same sample. Another challenge for liquid biopsy studies for early detection is that any individual cancer type is rare in a screening population. One strategy being explored is developing liquid biopsies for detecting multiple cancer types, or multi-cancer early detection (MCED) tests.

Before liquid biopsy-based assays can be used for cancer screening, they must be evaluated to demonstrate that these assays work in the biomarker screening pipeline including determining how well the assay distinguishes persons with clinical cancer diagnosis compared with no cancer (diagnostic performance study); how well the assays predict the development of clinical cancer among asymptomatic individuals (prediagnostic performance study); and how well the assay preforms in a clinical utility cancer screening trial. While several liquid biopsy technologies have been examined for distinguishing individuals with cancer, fewer studies have examined the prediagnostic performance in asymptomatic individuals who may be targets for cancer screening and can benefit the most from clinical interventions. The most efficient way to accomplish these studies is to use stored samples that are collected prior to cancer diagnosis. To advance this field, partnerships need to be encouraged between technology developers and population-based researchers (including cohort and biorepository researchers), to facilitate these biomarker investigations in the appropriate populations with the optimal study design.

Research Objectives

Through this NOSI, NCI encourages applications that investigate the use of existing cohort samples and samples from ongoing prospective collections for analytical and clinical validation of assays for earlier detection of cancer.

Research areas of interest for this NOSI include but are not limited to:

• Facilitate the development of high-throughput, sensitive assay methods to identify, verify and validate biomarkers that are useful in early detection of early-stage cancers or their lethal precursors
• Develop, evaluate, verify, quantify, or validate promising liquid biopsy-based biomarkers in various risk populations for effective cancer detection of early-stage cancers
• Determine the sensitivity and specificity of liquid biopsy assays to detect one or more cancers in prediagnostic specimens
• Determine relationship between algorithm cut-points for a positive assay result depending upon the risk level of the population for which the assay is being used for cancer screening

• Demonstrate ability to distinguish between individuals at risk of developing lethal vs. non-lethal clinical cancers
• Develop early detection models based on longitudinal patterns of the biomarkers using serial biospecimens

• Describe the natural history of a biomarker to determine the timeline of detection prior to clinical cancer diagnosis or through the transition from early stage to advanced stage cancer using serial biospecimens.
• Evaluate the utility of a specified liquid biopsy early cancer detection, or detection prior to clinical cancer diagnosis, using prediagnostic specimens from asymptomatic individuals
• Demonstrate usability of a liquid biopsy assay in clinical settings considering standard protocols (i.e., sample collection, transportation, handling, and storage of samples)

NCI has a history of supporting cohorts and biorepositories that can be identified through the DCP Biorepositories, DCCPS funded cohorts, the NCI Cohort Consortium, the Early Detection Research Network, and a searchable list of cohorts through the NCI Cancer Epidemiology Descriptive Cohort Database (CEDCD). Other catalogues that list potential cohorts or biorepository researchers include the NCI Specimen Resource Locator (SRL) or NHLBI Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC).

Applications Not Responsive to this FOA

The following types of studies are not responsive to this FOA. Applications proposing such studies will be considered non-responsive and will not be reviewed.

• Biomarker studies that are not focused on early detection of cancer
• Biomarker studies that are focused on monitoring cancer progression and/or treatment
• Biomarker studies that are focused on reoccurrence

Application and Submission Information

This notice applies to due dates on or after January 5, 2023, and subsequent receipt dates through July 02, 2025.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-CA-23-004” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
• All applicants are strongly encouraged to contact the NCI program contacts, listed below, to discuss the specific aims of the application before submission

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Matthew Young, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5846
Email: matthew.young@nih.gov

Leah E. Mechanic, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-6847
Email: mechanil@mail.nih.gov

Xing-Jian Lou, Ph.D. (for SBIR/STTR inquiries)
National Cancer Institute (NCI)
Telephone: 240-276-5226
Email: loux@mail.nih.gov

Financial/Grants Management Contact(s)

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
E-mail: hines@mail.nih.gov