[Federal Register Volume 82, Number 147 (Wednesday, August 2, 2017)]
[Notices]
[Pages 35976-35978]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-16203]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Request for Letters of Interest for NCI-MATCH Laboratories

SUMMARY: The National Cancer Institute (NCI) in collaboration with the 
NCI Molecular Analysis for Therapy Choice (MATCH) trial leadership (NCT 
02465060) 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 MATCH trial. The NCI MATCH trial has 
implemented a new process for identifying patients for arms with rare 
variant eligibility criteria. Laboratories will contact any of the 
approximately 1100 sites that have activated NCI MATCH if a specimen 
sent from one of these sites has a rare variant that would potentially 
make the patient eligible for one of the treatment arms open in this 
initiative.

DATES: LOIs should be submitted to the National Cancer Institute (NCI), 
National Institutes of Health (NIH) on or before 5:00 p.m. EST on 
January 31, 2018.

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: NCI-MATCH aims to establish whether patients 
with tumor mutations, amplifications or translocations in one of the 
genetic pathways of interest are likely to derive clinical benefit 
(primary objective: Objective response; secondary objective: 
Progression-free survival of at least 6 months) if treated with agents 
targeting that specific pathway in a single-arm design (see current 
arms below).
    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. Further information about the NCI-MATCH trial may be found at 
http://ecog-acrin.org/trials/nci-match-eay131.
    The selected collaborating laboratories may only act (i.e., refer 
patients) on any of the rare 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.
    CLIA accredited/certified laboratories located in the United States 
may be

[[Page 35977]]

considered for addition to the laboratory network.

Letter of Interest (LOI) and Collaboration 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 per month
 Number of patients whose assay results would make them 
potentially eligible for the rare variant arms (below) in the last 6 
months
 Willingness to contact sites regarding results with a rare 
variant potentially eligible for NCI MATCH
 Willingness to sign a collaboration agreement with NCI and to 
share data and publication rights
 Which arms the laboratory is prepared to address.

    The arms that are included in the rare variant protocol amendment 
are:

----------------------------------------------------------------------------------------------------------------
             Rare variant candidate                                 MATCH subprotocol (agent)
----------------------------------------------------------------------------------------------------------------
AKT1 mut.......................................  EAY131-Y (AZD5363).
NF2 loss.......................................  EAY131-U (Defactinib).
MET amplification..............................  EAY131-C1 (Crizotinib).
BRAF V600......................................  EAY131-H (Dabrafenib + Trametinib).
SMO/PTCH1......................................  EAY131-T (Vismodegib).
BRAF non V600..................................  EAY131-R (Trametinib).
EGFR T790M.....................................  EAY131-E (AZD9291).
ALK translocation..............................  EAY131-F (Crizotinib).
cKIT mutation..................................  EAY131-V (Sunitinib).
EGFR mutation..................................  EAY131-A (Afatinib).
ROS1 translocation.............................  EAY131-G (Crizotinib).
GNAQ/GNA11.....................................  EAY131-S2 (Trametinib).
MET exon 14 skipping...........................  EAY131-C2 (Crizotinib).
NTRK fusions...................................  EAY131 Z1E (Loxo101).
MTOR mutations.................................  EAY131-L (MLN0128).
TSC1 or TSC2 mutations.........................  EAY131-M (MLN0128).
CCND 1,2,3 amplifications......................  EAY131-Z1B (Palbociclib).
CDK4 or CDK6 amplification.....................  EAY131-Z1C (Palbociclib).
DDR2 mutation..................................  EAY131-X (Dasatinib).
----------------------------------------------------------------------------------------------------------------

    Following an acceptable eligibility review to the NCI MATCH 
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 in which the lab has 
interest. The lab would then be required to submit an application 
within 3 months for review by the NCI-MATCH steering 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 must be on tumor tissue only (including lymphoma 
and myeloma). Assays using circulating nucleic acids will not be 
accepted at this time.
     Laboratory NGS panels must be analytically and clinically 
validated, 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 MATCH)
[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 Rare 
Variant Arms (see table above). Applicant laboratories must state the 
MATCH arms in which they would like to participate.
     Academic laboratories must be located at a center that 
participates in NCI MATCH.
     As it is important that the dataset used for analysis in 
NCI MATCH be as robust as possible, the laboratory NGS test will 
require qualification, during which the performance of the laboratory 
will be compared with the NCI-MATCH central laboratory test to ensure 
good agreement with that assay. Concordance between the results from 
each lab and results of the NCI MATCH NGS assay run on an archived 
specimen will be tracked; if concordance falls below 90% for SNVs and 
indels, or 80% for CNVs, the laboratory must be willing to address 
these issues with the NCI MATCH team. If they cannot be addressed to 
the satisfaction of the NCI MATCH team, the laboratory may be 
eliminated from participation in NCI MATCH.
     Laboratories shall NOT advertise that they are screening 
laboratories for MATCH eligibility. Any press release or public 
disclosure requires clearance by NCI and NCI MATCH.
     Laboratories must agree to use the existing workflow 
established by the NCI MATCH trial to identify patients for the Rare 
Variant Arms. This includes use of the MATCH Rare Variant

[[Page 35978]]

template to identify aMOIs for submission to MATCHbox.

[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 MATCH.
[cir] Laboratories must notify NCI MATCH sites that the laboratory 
results would potentially allow the patient to be eligible for NCI 
MATCH.
[cir] Laboratories must track how many assays per week detect rare 
variants that could make a patient eligible for NCI MATCH.
    [cir] If the clinician presents the MATCH study and the patient is 
eligible and desires to enter the study, the laboratory must agree to 
fill out a spreadsheet that can be used to put the results into the 
informatics system that assigns treatment in NCI MATCH (MATCHbox).
    [cir] Laboratories must have a way to answer questions from NCI 
MATCH sites about their assay and must have a contact person for 
optimal communication with the NCI MATCH 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 
MATCH trial (https://ctep.cancer.gov/branches/rab/intellectual_property_optionto_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 MATCH 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 Collaboration Agreement'' to 
[email protected].
    2. LOIs will be accepted until January 31, 2018 at 5:00 p.m. 
Eastern Time. LOIs will be reviewed on a monthly basis, with those 
arriving by the 15th day of the month being reviewed and answered by 
the 15th day of the following month.
    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 3 months of 
notification of acceptance will be de-activated, and a new LOI must 
then be submitted if the laboratory wishes to participate in NCI MATCH.
    5. DO NOT send a full application until you are invited to do so.
    Review criteria for LOI:
     Laboratory is a CLIA certified or accredited laboratory 
within the United States.
     Academic laboratories must have NCI MATCH open at their 
site.
     Laboratory has adequate sensitivity, specificity.
     Laboratory tests tumor tissue for rare variants as 
described in NCI MATCH.
     Laboratory agrees to provide needed information for 
evaluation of the analytical validity of the test.
     Laboratory is likely to refer at least 100 patients to NCI 
MATCH based on detection of rare variants in the past.
     Laboratory agrees to contact sites regarding NCI MATCH 
eligibility.
     Laboratory agrees to a collaboration with NCI as detailed 
above.
    Review criteria for full application:
     Laboratory NGS assay interrogates inclusionary and all 
exclusionary variants for arms in which the laboratory will 
participate.
     Laboratory supplies evidence that the assay meets 
analytical requirements as detailed above.
     Laboratories are capable of contacting clinical sites, 
tracking activity, and of referring at least 100 patients to the study 
based on detection of rare variants in the past.
     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 MATCH study and to collaborate fully with the MATCH team.
    For more information, contact [email protected].

    Dated: July 20, 2017.
James V. Tricoli,
Chief, Diagnostic Biomarkers and Technology Development Branch, Cancer 
Diagnosis Program, Division of Cancer Treatment and Diagnosis, National 
Cancer Institute.
[FR Doc. 2017-16203 Filed 8-1-17; 8:45 am]
 BILLING CODE 4140-01-P