[Federal Register Volume 85, Number 48 (Wednesday, March 11, 2020)]
[Notices]
[Pages 14210-14212]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-04916]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Request for Letters of Interest (LOI) for Pediatric Focused NCI-
MATCH Laboratories

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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SUMMARY: The National Cancer Institute (NCI) through its National 
Clinical Trials Network (NCTN) is developing a successor precision 
medicine trial to `NCI-Molecular Analysis for Therapy Choice (NCI-
MATCH)' entitled `NCI-ComboMATCH'. The principal of this intiative is 
to overcome drug resistance to single-agent therapy by developing 
genomically-directed targeted agent combinations. All combinations must 
be supported by robust, preclinical in vivo evidence.
    NCI-ComboMATCH trial leadership invites applications for Clinical 
Laboratory Improvements Program (CLIA) certified/accredited 
laboratories that test tumor specimens from pediatric patients 
utilizing Next-Generation Sequencing (NGS) assays to participate in the 
NCI-ComboMATCH trial. In order to support this trial, the designated 
laboratories participating in NCI-ComboMATCH will identify pediatric 
patients for the specific variants needed for trial eligibility. 
Laboratories will be

[[Page 14211]]

required to contact any of the NCTN sites that have activated NCI-
ComboMATCH if a specimen sent from one of these sites has a variant(s) 
that would potentially make the patient eligible for one of the 
treatment arms.

DATES: Letters of Interest (LOIs) should be submitted to the National 
Cancer Institute (NCI), National Institutes of Health (NIH) on or 
before 5:00 p.m. EST on June 30, 2020.

ADDRESSES: Submit LOIs by email to [email protected]. 9609 
Medical Center Drive, 3 West, Room 526, MSC 9728, Rockville, MD 20892.

FOR FURTHER INFORMATION CONTACT: Questions about this request for LOIs 
should be directed to [email protected]. James V. Tricoli 
[email protected] can also provide further information.

SUPPLEMENTARY INFORMATION: In accordance with 42 U.S.C. 285, of the 
Public Health Service Act, as amended. Similar to NCI-MATCH, NCI-
ComboMATCH is conceived as a signal-seeking study. The NCI-ComboMATCH 
team will determine whether pediatric patients with tumor mutations, 
amplifications or translocations in the genetic pathway(s) of interest 
are likely to derive clinical benefit if treated with a combination of 
precision medicine agents targeting those specific pathway(s). This 
recruitment is for pediatric focused labs that can specifically screen 
250 pediatric patients seen at NCTN sites per month.
    Patients with histologically documented solid tumors and lymphomas 
whose disease has progressed following at least one line of standard 
systemic therapy or for whom no standard therapy exists are eligible if 
they meet the eligibility criteria for the trial.
    The selected collaborating outside laboratories may only act (i.e. 
refer patients) on any of the variant arms for which their assay 
reports actionable mutations of interest (aMOIs). The assay must also 
report all exclusionary variants for the arm unless these occur at a 
frequency of <1% in cancer patients.
    Only CLIA accredited/certified laboratories located in the United 
States may be considered for addition to the laboratory network.

Letter of Interest (LOI) and Confidentiality Agreement

    Candidate laboratories should submit a letter of interest to 
[email protected] stating:

 Statement of interest in the proposed activity
 Laboratory name
 Lead contact name, address, email address, and telephone 
number
 CLIA certification number
 Assay name
 Brief description of assay
    [cir] Sensitivity and specificity for SNVs, indels, CNV, fusions
    [cir] Method of analysis
    [cir] Platform and variant calling
 Number of assays on pediatric patients per month
 Number assays on patients seen at NCTN study sites per month
 Provide a list of other CLIA approved/certified tests that 
have been validated in your laboratory
 Willingness to contact sites regarding results with a 
potentially eligible for NCI-ComboMATCH
 Willingness to sign a collaboration agreement with NCI 
(https://ctep.cancer.gov/branches/rab/intellectual_property_option_to_collaborators.htm) and to share data 
and publication rights

    Following an acceptable eligibility review to the NCI-ComboMATCH 
screening committee, the laboratory would execute a confidentiality 
agreement with the NCI and will be provided with a detailed list of 
eligibility and exclusion variants for arms (approved at that time). 
The lab would then be required to submit an application within 6 weeks 
for review by the NCI-ComboMATCH review committee. Candidate 
laboratories will be required to meet the following general 
requirements:
     Testing must be performed in a CLIA-certified or -
accredited laboratory located in the United States.
     Assays can be on tumor tissue (including lymphoma) or 
circulating tumor DNA (ctDNA).
     Laboratory NGS panels must be analytically and clinically 
validated on DNA from human tumor tissues, with performance 
characteristics as follows:

    [cir] Specificity at least 99% for single nucleotide variants, 
indels
    [cir] Sensitivity at least 95% for single nucleotide variants, 
indels
    [cir] Sensitivity of 90% for copy number variants (state fold of 
copy number variants that can be detected with 90% sensitivity)
    [cir] 99% reproducibility between sequencers (if more than one 
sequencer is used) and between operators
    [cir] Lower limit of detection for SNV, indels, CNV must be stated.

    Laboratories must supply the following information in their 
application:

    [cir] Lower limit of % tumor accepted, and whether (and which) 
enrichment procedures are employed
    [cir] Whether the lab archives images of slides from the tumor
    [cir] Whether the lab also runs germline as well as tumor with the 
assay (a simultaneous germline sequencing is not required by NCI-
ComboMATCH)
    [cir] A detailed description of assay procedures, including 
starting material, extraction of nucleic acids, quality assurance, 
quality metrics, data analysis and filters must be supplied.

     Laboratory NGS test panels must interrogate actionable 
mutations of interest (aMOIs) required for enrollment into the 
available variant arms. Applicant laboratories must state which NCI-
ComboMATCH arms they would like to participate in.
     Academic laboratories must be located at a center that 
participates in NCI-ComboMATCH.
     The designated lab should be willing to provide residual 
nucleic acid from the sample they tested if the patient enrolls on NCI-
ComboMATCH.
     Laboratories shall NOT advertise that they are screening 
laboratories for ComboMATCH eligibility without prior review by NCI and 
ECOG-ACRIN. Any press release or public disclosure requires clearance 
by NCI and the NCI-ComboMATCH team.
     Laboratories must agree to use the existing workflow 
established by the NCI NCI-ComboMATCH trial team to identify patients 
for the variant arms.
    [cir] Laboratory results of NGS assays done for clinical care will 
be the subject of this initiative. There is no funding for 
``screening'' a patient for NCI-ComboMATCH.
    [cir] Laboratories must notify NCI-ComboMATCH sites that the 
laboratory results would potentially allow the patient to be eligible 
for NCI Combo MATCH.
    [cir] Laboratories must track how many assays per month detect 
variants that could make a pediatric patient eligible for NCI-
ComboMATCH.
    [cir] If the clinician presents the NCI-ComboMATCH study and the 
pediatric patient is eligible and desires to enter the study, the 
laboratory must agree to enter results into the informatics system that 
assigns treatment in Combo MATCH (MATCHbox).
    [cir] Laboratories must have a way to answer questions from Combo 
MATCH sites about their assay and must have a contact person for 
optimal communication with the NCI-ComboMATCH team.

[[Page 14212]]

     Prior to participation, laboratories must enter into a 
collaboration agreement with NCI. A sample agreement is available upon 
request. As part of such a collaboration agreement, laboratories must 
agree to provide the licensing rights described in the CTEP IP Option 
to the Pharmaceutical Collaborators who provided agents for the NCI-
ComboMATCH trial (https://ctep.cancer.gov/branches/rab/intellectual_property_option_to_collaborators.htm) as well as agree to 
the data sharing and publication rights consistent with those 
agreements.
     No reimbursement for these activities (testing or 
notification of sites of NCI-ComboMATCH eligibility) exists.
    Qualified laboratories serving underserved populations are 
encouraged to participate.
    How to apply:
    1. Submit letter of interest (LOI) as described above under 
``Letter of Interest and Confidentiality Agreement'' to 
[email protected].
    2. LOIs will be accepted for 3 months from the date of this notice. 
LOIs will be reviewed immediately upon receipt.
    3. Notification of acceptance, non-acceptance or questions from 
Steering Committee will be sent to the designated contact person as 
soon as the LOI has been reviewed. This notification will include 
further instructions if a full application is invited.
    4. Applications that have not been submitted within 6 weeks of 
notification of acceptance of the LOI will be de-activated and not 
further considered.
    5. DO NOT send a full application until you are invited to do so.
    Review criteria for LOI:
    Laboratory is a CLIA certified laboratory within the United States.
    Academic laboratories must have NCI-ComboMATCH open at their site.
    Laboratory NGS assay has adequate sensitivity and specificity.
    Laboratory tests tumor tissue for variants as described in NCI-
ComboMATCH.
    Laboratory agrees to provide needed information for evaluation of 
the analytical validity of the test.
    Laboratory is likely to screen at least 250 pediatric patients at 
NCTN sites for NCI-ComboMATCH per month.
    Laboratory agrees to contact sites regarding NCI-ComboMATCH 
eligibility.
    Laboratory agrees to a collaboration with NCI as detailed above.
    Review criteria for full application:
    Laboratory supplies evidence that the assay meets analytical 
requirements as detailed above.
    Laboratories are capable of contacting clinical sites, tracking 
activity, and of screening at least 250 pediatric patients at NCTN 
sites per month to the study based on detection of potential variants.
    Laboratories agree to execute a collaboration agreement with NCI, 
as well as to data sharing and sharing publication rights.
    Laboratories agree to abide by the procedures in place for the NCI-
ComboMATCH study and to collaborate fully with the NCI-ComboMATCH team.
    For more information, contact [email protected].

    Dated: March 5, 2020.
James V. Tricoli,
Chief, Diagnostic Biomarkers and Technology Branch, Cancer Diagnosis 
Program, National Cancer Institute.
[FR Doc. 2020-04916 Filed 3-10-20; 8:45 am]
 BILLING CODE 4140-01-P