[Federal Register Volume 88, Number 155 (Monday, August 14, 2023)]
[Notices]
[Pages 55055-55057]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-17352]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Request for Letters of Interest (LOI) for NCI-ComboMATCH 
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) has developed a successor precision 
medicine trial to `NCI-Molecular Analysis for Therapy Choice (NCI-
MATCH)' entitled `NCI-ComboMATCH'. The principle of this initiative 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.

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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 September 30, 2023.

ADDRESSES: Submit LOIs by email to [email protected]. 9609 
Medical Center Drive, 3 West, Room 360, Rockville, MD 20892.

FOR FURTHER INFORMATION CONTACT: Questions about this request for LOIs 
should be directed to [email protected] or Benjamin Kim at 
benj[email protected] or by phone at (240) 276-5961.

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. These laboratories are required to have a catchment area that 
serves underrepresented populations and should be able to provide 
documentation of the proportion of subjects seen by the lab by race/
ethnic origin. Laboratories serving a large percentage (>30%) of 
African Americans, Native Americans, Hispanics, Asians and Pacific 
Islanders will be considered. In order to support this trial, the 
designated laboratories participating in NCI-ComboMATCH will identify 
patients for the specific molecular variants needed for trial 
eligibility. Laboratories will be asked to indicate on their report if 
a patient is eligible for one of the NCI-ComboMATCH subprotocols. If 
this is not feasible the lab is asked to contact the patients provider 
via letter, email or fax that the individual may be eligible for a NCI-
ComboMATCH subprotocol if a specimen sent from the lab has a variant(s) 
that would potentially make the patient eligible for one of the 
treatment arms. Physicians will also be able to refer the patient 
directly to the NCI-ComboMATCH registration trial. In any of these 
cases, the laboratory will be required to provide the variant data to 
the NCI-ComboMATCH `MATCHbox' which is a computer program that serves 
to gather information used to determine the eligibility of the 
particular patient to a treatment arm.
    In accordance with 42 U.S.C. 285, of the Public Health Service Act, 
as amended. Like 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 laboratories in areas 
serving underrepresented populations that can screen at least 100 
patients per month.
    Patients with histologically documented solid tumors 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-
ComboMATCH trial may be found at https://ecog-acrin.org/clinical-trials/eay191-combomatch/.
    The selected collaborating outside laboratories may only 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
 Proportion of underrepresented groups or populations tested by 
the lab
 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 patients per month
 Willingness to report to or contact providers of patients who 
are potentially eligible for one of the subprotocols on NCI-ComboMATCH
 Willingness to sign a collaboration agreement with NCI 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 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 by September 
30th, 2023 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 may be on tumor tissue or circulating nucleic 
acids.
     Laboratory NGS panels must be analytically and clinically 
validated on DNA from human tumor tissue, 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 SNVs, indels, and CNVs must be 
stated;
    [cir] Laboratories should also provide these parameters if they 
have a validated circulating tumor DNA (ctDNA) assay;
    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 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.
     The designated lab should be willing to provide residual 
nucleic acid from the sample they tested if the patient enrolls on NCI-
ComboMATCH.
     As it is important that the dataset used for analysis in 
NCI-ComboMATCH 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-ComboMATCH Central Laboratory test to 
ensure good agreement with that assay.
     Laboratories shall NOT advertise that they are screening 
laboratories for

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ComboMATCH eligibility without prior review by NCI and ECOG-ACRIN. Any 
press release or public disclosure requires clearance by NCI and NCI-
ComboMATCH regulatory team.
     Laboratories must agree to use the existing workflow 
established by the 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-ComboMATCH.
    [cir] Laboratories must track how many assays per month detect 
variants that could make a 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 the results into the informatics system that assigns 
treatment in NCI-ComboMATCH (MATCHbox).
    [cir] Laboratories must have a way to answer questions from NCI-
ComboMATCH 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 and includes the requirement to participate in trial monitoring 
by NCI, the trial sponsor. 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) (https://www.gpo.gov/fdsys/pkg/FR-2011-03-11/pdf/FR-2011-03-11.pdf) 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 a large component of an 
underrepresented population are the only ones being considered for this 
Federal Register Notice.
    How to apply:
    1. Submit letter of interest (LOI) as described above under 
``Letter of Interest and Confidentiality Agreement'' to 
[email protected].
    2. LOIs must be submitted to the National Cancer Institute (NCI), 
National Institutes of Health (NIH) on or before 5:00 p.m. EST on 
September 30, 2023. 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 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.
    Laboratory is able to provide evidence that its volume of patients 
tested is composed >30% underrepresented peoples.
    Laboratory NGS assay has adequate sensitivity and specificity.
    Laboratory tests tumor tissue for variants required for NCI-
ComboMATCH.
    Laboratory agrees to provide needed information for evaluation of 
the analytical validity of the test.
    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 providers and tracking 
activity 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: August 8, 2023.
Lyndsay N. Harris,
Associate Director, Cancer Diagnosis Program, Division of Cancer 
Treatment & Diagnosis, National Cancer Institute.
[FR Doc. 2023-17352 Filed 8-11-23; 8:45 am]
BILLING CODE 4140-01-P