Request for Information (RFI): Nomination of Molecular Targets Substantially Relevant to the Growth or Progression of Pediatric Cancers
Release Date: April 10, 2018
National Cancer Institute (NCI)
Title V of the Food and Drug Administration (FDA) Reauthorization Act (FDARA) of 2017 assigns the National Cancer Institute (NCI) a collaborative role with FDA in establishing, publishing, and regularly updating a list of molecular targets considered on the basis of data the FDA determines to be adequate, to be substantially relevant to the growth and/or progression of pediatric cancers, and that may trigger the requirement for pediatric investigations [21 USC 355c (m)(1)(A)]. Molecular targets that are considered ?not relevant? to the growth and/or progression of pediatric cancers will be placed on a second list [21 USC 355c (m)(1)(B)]. The purpose of this Request for Information (RFI) Notice is to solicit nominations for molecular targets that may be considered substantially relevant to the growth and/or progression of pediatric cancers. Information collected through this RFI will be used to inform decision-making lists of molecular targets specified in Title V of FDARA. The independent non-profit organization Friends of Cancer Research prepared a discussion document with input from a multi-stakeholder working group representing a broad cross-section of the pediatric cancer community that addressed issues related to the establishment of lists of pediatric-relevant molecular targets. Respondents to this RFI are encouraged to review the document found at https://www.focr.org/sites/default/files/pdf/FINAL_DiscussionDoc.pdf for relevant background information, including a discussion of the utility of classifying molecular targets in cancer by subtype when assessing their relevance to pediatric cancers. The molecular target subtypes described in the document are listed below:
- Gene abnormality-based targets: These are targets that are the result of specific gene abnormalities (e.g., BCR-ABL1) or that are present in a critical biologically-related pathway of a gene abnormality (e.g., MEK for BRAF gene fusions) or that exhibit a synthetic lethal relationship to a gene abnormality (e.g., PARP for BRCA1/2 mutations).
- Cancer cell lineage-based targets: These are targets that are intrinsic to the cancer cell lineage or developmental stage (e.g., CD19, CD20, GD2, etc.).
- Tumor microenvironment and immunotherapy-based targets: These are targets that may be identified in non-cancer cells of the tumor microenvironment and/or that may be involved in modulating the immune system response to the cancer.
- Other targets: A final category is that of targets present in the cancer cells that do not show cancer-specific genetic alterations (e.g., tubulin, heat-shock proteins, etc.).
All stakeholders with an interest in improving the outcomes of childhood cancers through the identification and development of more effective targeted agents are invited to provide information. Your response may mention your membership and/or affiliation within an industry, government, or academic entity/organization/institution. A document with a list of candidate targets for which input on pediatric relevance is solicited is available at https://www.fda.gov/Drugs/NewsEvents/ucm599165.htm. These candidate targets are classified using the subtypes described above. Input regarding targets that are not on the list but that may be relevant to pediatric cancers is of particular interest as is feedback on targets that are on the list but that may not be appropriate for inclusion on the list. For each target that is nominated (or endorsed) for inclusion on the list, NCI is seeking information that includes, but is not limited to, the areas listed below. Please include references when published data are cited.
- Genomic data that support the relevance of the proposed target to pediatric cancers.
- RNA and protein expression data that support the relevance of the proposed target to pediatric cancers.
- In vitro data that support that support the relevance of the proposed target to pediatric cancers.
- In vivo data that support the relevance of the proposed target to pediatric cancers.
- Clinical experience that supports the relevance of the proposed target to pediatric cancers.
Submitting a Response
All responses must be submitted to firstname.lastname@example.org by May 20, 2018. Please include the Notice number in the subject line. Response to this RFI is voluntary. Responders are free to address any or all of the categories listed above. The submitted information will be reviewed by NIH staff and will be shared with FDA staff. Please do not include any proprietary, classified, confidential, and/or sensitive information in your response. The NIH will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder's submission. The collected information may appear in reports and may be shared publicly on an NIH or FDA website. The Government reserves the right to use any non-proprietary technical information in summaries of the state-of-the-science, and any resultant solicitation(s). This RFI is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Federal Government, the National Institutes of Health (NIH), or individual NIH Institutes and Centers, including the NCI. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government?s use of such information.
Please direct all inquiries to:
Malcolm A. Smith, M.D., Ph.D.
National Cancer Institute (NCI)