[Federal Register Volume 85, Number 126 (Tuesday, June 30, 2020)]
[Notices]
[Pages 39198-39199]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-14043]


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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; extension.

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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. Due to the 
coronavirus pandemic the NCI is providing an extension of the 
previously published notice in the Federal Register on March 11, 2020, 
to allow candidate more time to submit LOIs.

DATES: The due date for Letters Of Interest (LOIs) has been extended 
and should now be submitted to the National Cancer Institute (NCI), 
National Institutes of Health (NIH) on or before 5:00 p.m. EST on 
September 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, 
at 240-276-5725 or [email protected], can also provide further 
information.

SUPPLEMENTARY INFORMATION: NCI-ComboMATCH trial leadership invites 
applications for Clinical Laboratory Improvements Program (CLIA) 
certified/accredited laboratories that test tumor specimens from 
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 patients for the specific variants needed for trial 
eligibility. Laboratories will be 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.
    This notice was previously published in the Federal Register on 
March 11, 2020, page 14208-14210 (85 FR 14208). The purpose of this 
notice is to allow an additional 90 days for submission of the LOI. The 
due date for LOI submission has been extended from the previous date of 
June 30, 2020 to September 30, 2020 to allow more labs to submit. This 
is necessary due to the impact of the coronavirus pandemic. 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 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, lymphomas and 
multiple myeloma 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
 What other CLIA approved/certified tests 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 2 months 
for review by the NCI-ComboMATCH review committee. Candidate 
laboratories will

[[Page 39199]]

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 rare 
variants that could make a pediatric patient eligible for NCI-
ComboMATCH.
    [cir] If the clinician presents the NCI-ComboMATCH study and the 
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.

     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 rare 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: June 24, 2020.
James V. Tricoli,
Chief, Diagnostic Biomarkers and Technology Branch, Cancer Diagnosis 
Program, National Cancer Institute.
[FR Doc. 2020-14043 Filed 6-29-20; 8:45 am]
BILLING CODE 4140-01-P