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NIH/NCI 458 – Microbiome-Based Tests for Cancer Research, Diagnosis, Prognosis and/or Patient Management

Fast-Track proposals will NOT be accepted.

Direct-to-Phase II proposals will NOT be accepted.

Number of anticipated awards: 4-6

Budget (total costs, per award):

Phase I: up to $400,000 for up to 12 months

Phase II: up to $2,000,000 for up to 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.


Summary

This proposal is for the development of microbiome-based technologies for cancer research, diagnosis, and patient management (e.g., prognosis, treatment assignment, and efficacy monitoring). Although early and accurate diagnosis is key to successful treatment, effective methods for early detection do not exist for many cancers. Indeed, the available diagnostic tests are characterized by either high false positive rates due to low specificity resulting in unnecessary surgeries for diagnostic confirmation (e.g., CT scan for lung cancers) and/or high false negative rates due to low sensitivity (e.g., CA125 and trans-vaginal ultrasound for ovarian cancers). For example, the sole FDA-approved biomarker for pancreatic cancer, serum CA19-9, is mostly used for disease monitoring rather than screening due to inherent limits in specificity as its levels can be elevated in several other concomitant conditions. Other types of diagnostics using liquid biopsies can detect cell-free-circulating DNA (ctDNA) derived from tumors in late-stage cancers (stages III and IV), as traditional ctDNA-based analyses lack the sensitivity required to detect small tumors/early lesions. Furthermore, accurate technologies are also needed for cancer prognosis, treatment assignment, and efficacy monitoring. In addition to addressing the specificity/sensitivity issues of the currently available approaches, microbiome-based technologies would ideally be capable of using liquid biopsies that are safer, more cost-effective, and faster to obtain than solid biopsies for a wider adoption in clinics. Recently, the microbiome was added to the list of cancer hallmarks and multiple clinical and preclinical studies have revealed an association of specific microbiome signatures with individual cancers and with response to therapy (chemotherapy, immunotherapy, and radiotherapy). In addition, recent advances integrating the analysis of large datasets from next-generation DNA sequencing, and new methods of computational modeling using AI and machine learning, have shown the feasibility of using microbial biomarkers for early cancer detection, and personalized medicine. Thus, the development of microbial signatures from cancer patient samples, ideally from liquid biopsies, to be used alone or in combination with other biomarkers, offers an exciting opportunity to develop new and innovative tools for better cancer diagnosis, prognosis, and patient management. These technologies using microbial signatures as biomarkers for cancer detection and patient management will also enable researchers to better understand the fundamental underlying biology and molecular dynamics of microbe-tumor interactions as the causes and roles of microbial changes associated with cancer are not well understood.

Project Goals

The short-term goal for this topic is to develop new and innovative tests (kits or services) for early cancer detection/diagnosis, prognosis and/or treatment assignment and monitoring to be used in research. The mid- and long-term goals are, respectively, to provide to the clinical community microbiome-based CLIA tests (laboratory-developed or research use only tests) and FDA-approved diagnostic or companion diagnostic tests. Activities that fall within the scope of this solicitation include the development of tests (kits or services) for early cancer diagnosis, prognosis, treatment assignment and/or monitoring, and/or cancer research that identify and use microbial signatures (presence, absence, and/or abundance of certain microbes) of different types (DNA and/or RNA, proteins, metabolites), alone or in combination with host molecular markers. The microbial signature can be bacterial alone or include other microbes (e.g., fungi and viruses). These technologies should show some improvements (e.g., safer technologies using noninvasive biopsies, more cost-effective, better accuracy, more user-friendly) compared to the current existing methods. They may include, but not be limited to, electromechanical sensors, hybridization or PCR technology other than sequencing to be faster and more affordable for a wider adoption in different clinical settings. 

Phase I Activities and Deliverables:

Phase I activities should generate scientific data confirming the clinical potential of the proposed technology. The phase I research plan must contain specific, quantifiable, and testable feasibility milestones.

Expected activities and deliverables include:

  • Provide data of the verification and optimization study of the proposed technology using clinical samples collected from the population of interest including:
    • The assay performance characteristics (e.g., sensitivity, specificity and reproducibility); and
    • The strategy and data to:
      • Minimize the contribution of contaminants to microbial signatures by, for example, establishing protocols for sample collection, storage and molecular extraction, and/or bioinformatic decontamination analysis methods.
      • And/or correct for preanalytical variables such as different collection and storage methods.
  • Analytically validate the technology in a CLIA-certified laboratory (i.e., analytical sensitivity, specificity, LOD, repeatability) and describe the technical limitations of the technology.
  • Provide the technology workflow and the SOPs.
  • Establish QC and QA measures to ensure and maintain the quality of the results generated (accuracy and reproducibility).
    • Report the throughput of the technology and the cost per sample.
    • Establish a clinical validation plan/strategy:
    • Estimate the number of clinical samples (patients and controls) required for the clinical validation.
    • Establish a collaboration with a clinical cancer research site and/or a strategic business partner (e.g., a commercial CLIA-certified laboratory or a pharmaceutical company) to obtain sufficient clinical samples and a gold standard method/reference for technology validation.
    • Draft the study objectives and hypothesis.
    • In addition to the protocols, SOPs, and QC and QA measures established in phase I, describe the data collection strategy (retrospective or prospective study) and patient eligibility criteria.
    • Obtain all the regulatory approvals needed for the performance of the study using human samples.
  • Present Phase I results and future development plan to NCI staff.

Phase II Activities and Deliverables:

Phase II activities should support the commercialization of the technology, including but not limited by the following activities:

  • Conduct the clinical validation study in CLIA-certified laboratory(ies) for one potential use of the technology using the plan established in Phase I and report:
    • On what basis potentially eligible participants were identified (such as symptoms, results from previous tests, inclusion in registry).
    • Where and when potentially eligible participants were identified (setting, location, and dates).
    • Test undergoing validation, in sufficient detail to allow replication as well as the definition of and rationale for test positivity cut-offs or result categories of the test.
    • Rationale for choosing the reference standard (if alternatives exist). 
    • Reference standard, in sufficient detail to allow replication as well as definition of and rationale for test positivity cut-offs or result categories of the reference standard.
  • Provide the results (or at least some preliminary data) of the clinical validation study to potentially:
    • Demonstrate similar or superior assay performance (sensitivity, specificity, repeatability) compared to a reference standard.
    • Describe the clinical limitations of the test, if any, observed in the clinical validation study (e.g., disease, age, medication, time after meal ingestion, lifestyle habits [cigarette consumption, drug, alcohol, etc.]).
  • Benchmark the technology to the current existing methods in terms of clinical feasibility, cost, throughput, and safety.
  • Establish a product development strategy to obtain FDA regulatory approval for diagnostic test and/or a partnership/alliance with a strategic business partner (e.g., diagnostic or device company or a commercial clinical lab).
  • Present Phase II findings to NCI program staff.

 

Receipt date: November 14, 2023, 5:00 p.m. Eastern Standard Time

Apply for this topic on the Contract Proposal Submission (eCPS) website.

View the full PHS2024-1 Contract Solicitation.

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