EGFR Gene MutationPhase 1NCT02947386

Nimotuzumab and Nivolumab in Treating Patients With Advanced Non-small Cell Lung Cancer

A Phase 1 study testing Laboratory Biomarker Analysis, Nimotuzumab and Nivolumab in people with EGFR Gene Mutation and Recurrent Non-Small Cell Lung Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This phase I/II trial studies the best dose and side effects of nimotuzumab when giving together with nivolumab and to see how well they work in treating patients with non-small cell lung cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: EGFR Gene Mutation, Recurrent Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer
What is being tested?: Laboratory Biomarker Analysis, Nimotuzumab and Nivolumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 29 Jun 2017to 8 Sep 2022
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
Patients with pathologically confirmed non-small cell lung cancer
Patients must have had progressive NSCLC after first-line platinum-based chemotherapy for advanced disease
Have at least 3 months life expectancy
Have measurable disease per RECIST 1.1 criteria present
Patients with adenocarcinoma known to have anaplastic lymphoma kinase (ALK) rearrangements and/or epidermal growth factor receptor (EGFR) mutations that have had prior EGFR or ALK tyrosine kinase inhibitor therapy and have progressed, will also be eligible, regardless of line of therapy

Show all 17Show fewer

Phase I optional archival tissue/phase II mandatory archival tissue: able to provide enough biopsy tissue samples including primary diagnostic biopsy (archival), re-biopsy tissues (archival from time of disease progression/recurrence following first-line treatment failure) at disease progression to determine PD-L1 and EGFR expression and other biomarkers
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Platelets >= 100 x 10^9/L
Hemoglobin >= 9 g/dL
Serum creatinine =< 1.5 x institution upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 x ULN or =< 5 x ULN if liver metastases are present
Total serum bilirubin =< ULN; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's syndrome
Troponin-I, CK-MB +< BNP <200pg/ml
LVEF >= LLN
Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Who cannot join

Active autoimmune disease that has required systemic treatment in past 2 years; use of inhaled corticosteroids is allowed
Phase II only: history of other malignancies are allowed as long as the current disease stage that did not require active treatment with concomitant systemic cytotoxic chemotherapy, targeted therapy, investigational or biologic therapy (e.g., anti-CTLA4 or HER2 monoclonal antibodies) within 12 months prior to study registration and, is not likely to require systemic therapy in the next 12 months; hormone-related therapies (e.g., somatostatin analogues, etc.) are allowed on a case-to-case basis upon discussion with principal investigator
Active clinically serious infections requiring antibiotics, antiviral or antifungal agents
Symptomatic brain metastases; uncontrolled pleural effusion, seroperitoneum, or pericardial effusion
Has had any major surgery, chemotherapy, or radiotherapy within the previous 4 weeks; gamma knife radiosurgery for brain metastases within less than 2 weeks
Receiving other anti-cancer medical treatment during the study outside of the nimotuzumab or nivolumab

Show all 18Show fewer

Clinically significant interstitial pulmonary disease or known diagnosis of interstitial lung disease (ILD)
Has known immunosuppressive disease (e.g. human immunodeficiency virus [HIV], acquired immune deficiency syndrome [AIDS])
Patient has known hypersensitivity to the components of the study drugs or their analogs
Patient with uncontrolled cardiac disease or cardiac dysfunction, including any of the following:
History of uncontrolled angina pectoris that does not respond to medical intervention
Symptomatic pericarditis or myocardial infarction within 12 months prior to study entry that did not respond to treatment
History of documented congestive heart failure (New York Heart Association functional classification III or IV)
Documented cardiomyopathy
Uncontrolled hypertension defined by: systolic blood pressure (SBP) >= 160 mmHg and/or diastolic blood pressure (DBP) >= 100 mmHg
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Trial locations and contacts

1 site in 1 country.

United States1 site

Roswell Park Cancer Institute
Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase I/II Open-Label Study of Nimotuzumab in Combination With Nivolumab in Patients With Advanced Non-small Cell Lung Cancer

Read the detailed description

PRIMARY OBJECTIVES:

To determine the dose-limiting toxicities (DLT) and estimate the maximum tolerated dose (MTD) of nimotuzumab combined with nivolumab in the therapy of advanced non-small cell lung cancer (NSCLC) in order to establish the recommended phase II dose (RP2D). (Phase I)

II. To evaluate the 12 month overall survival of nimotuzumab in combination with nivolumab in patients with advanced NSCLC. (Phase II)

SECONDARY OBJECTIVES:

Examine the safety and tolerability profile of nivolumab in combination with nimotuzumab in NCSLC . (Phase I)

II. To evaluate the safety and the tolerability of nimotuzumab in combination with nivolumab using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). (Phase I)

III. Determine the immune analysis profile of nivolumab in combination with nimotuzumab. (Phase I)

IV. Examine the efficacy of the study combination utilizing irRECIST guidelines. (Phase I)

Overall response rate (ORR) per the immune-related Response Evaluation Criteria in Solid Tumors irRECIST. (Phase I)

VI. Progression-free survival (PFS) rate at 1 year. (Phase I)

VII. Progression-free survival (PFS). (Phase I)

VIII. Overall survival (OS). (Phase I)

IX. Disease control rate (DCR) and stable disease (SD). (Phase I)

To evaluate the safety profile of Nimotuzaumab in combination with Nivolumab in NCSLC using the CTCAE V. 4.

XI.To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: overall response rate (ORR) per irRECIST. (Phase II)

XII. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: progression-free survival (PFS) rate at 1 year. (Phase II)

XIII. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: progression-free survival (PFS). (Phase II)

XIV. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: overall survival (OS). (Phase II)

XV. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: disease control rate (DCR) and stable disease (SD). (Phase II)

TERTIARY OBJECTIVES:

Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and adverse events (AE). (Phase I)

II. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels; PD-L1 expression within both neoplastic and non-neoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and AE. (Phase I)

III. Comparison of response assessment criteria for a prospective analysis; irRECIST response assessment; irRC. (Phase I)

IV. Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and AE. (Phase II)

Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels. (Phase II)

VI. Examine the relationship of PD-L1 expression within both neoplastic and non-neoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and AE. (Phase II)

VII. Comparison of response assessment criteria for a prospective analysis; irRECIST response assessment; irRC. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of nimotuzumab followed by a phase II study.

Patients receive nivolumab intravenously (IV) over 60 minutes and nimotuzumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Conditions: EGFR Gene Mutation, Recurrent Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer
Being tested: Laboratory Biomarker Analysis, Nimotuzumab, Nivolumab
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Laboratory Biomarker AnalysisOther
Correlative studies
NimotuzumabBiological
Also called Thera-CIM-hr3, TheraCim hR3, Theraloc
Given IV
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV

Study groups in NCT02947386
Study group	Role	What they receive
Treatment (nivolumab, nimotuzumab)	Experimental	Patients receive nivolumab IV over 60 minutes and nimotuzumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Biological: Nimotuzumab; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

DLT as graded by NCI CTCAE version 4.0 (Phase I)
No formal analyses of DLTs are planned. Participants who do not have a DLT and who do not complete a full cycle of treatment will be considered non-evaluable for DLT.
Measured: Up to 28 days
ORR defined as complete response (CR) + partial response (PR) divided by number of patients as assessed by RECIST version 1.1 (Phase II)
Will be calculated as the number of patients with a confirmed complete or partial response divided by the total number of patients. The 95% confidence interval for ORR (CR + PR) will be presented based on the Wilson Score method as irRC response.
Measured: Up to 3 years

Secondary outcomes (1)

Incidence of adverse events assessed by NCI CTCAE version 4.0 (Phase I and II)
The frequency of AEs will be tabulated by grade across all dose levels and cycles. All patients who receive any study treatment will be considered evaluable for toxicity.
Measured: Up to 30 days after the last dose of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Jun 20178 Sep 2022

First posted27 Oct 2016 (estimated)
Study start29 Jun 2017
Primary completion15 Apr 2021
Study completion8 Sep 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for EGFR Gene MutationStudies of the same condition, open and under way.
More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02947386
Sponsor's protocol ID: I 281616
Other IDs: NCI-2016-01476, I 281616
Status last verified: Oct 2023
First submitted: 26 Oct 2016
Last updated: 5 Oct 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
A Study of VRN110755 in Patients With EGFR-Mutant Non-Small Cell Lung Cancer
EGFR-Mutant Non-Small Cell Lung Cancer
RecruitingPhase 3
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
PIK3CA Mutation, HER2- Negative Breast Cancer
RecruitingPhase 1/2
Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Solid Tumors
Active, not recruitingPhase 1
Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
EGFR-mutant Non-small Cell Lung Cancer
RecruitingPhase 3
A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Non-small Cell Lung Cancer, HER2 Mutation

All EGFR Gene Mutation trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Open-Label Study of Nimotuzumab in Combination With Nivolumab in Patients With Advanced Non-small Cell Lung Cancer
ClinicalTrials.gov ID: NCT02947386
Acronym / sponsor ID: I 281616
Conditions: EGFR Gene Mutation, Recurrent Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: Roswell Park Cancer InstituteUniversity, hospital or other
Study start: 29 Jun 2017 (actual)
Primary completion: 15 Apr 2021 (actual)
Study completion: 8 Sep 2022 (actual)
First posted: 27 Oct 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To determine the dose-limiting toxicities (DLT) and estimate the maximum tolerated dose (MTD) of nimotuzumab combined with nivolumab in the therapy of advanced non-small cell lung cancer (NSCLC) in order to establish the recommended phase II dose (RP2D). (Phase I)

II. To evaluate the 12 month overall survival of nimotuzumab in combination with nivolumab in patients with advanced NSCLC. (Phase II)

SECONDARY OBJECTIVES:

Examine the safety and tolerability profile of nivolumab in combination with nimotuzumab in NCSLC . (Phase I)

III. Determine the immune analysis profile of nivolumab in combination with nimotuzumab. (Phase I)

IV. Examine the efficacy of the study combination utilizing irRECIST guidelines. (Phase I)

Overall response rate (ORR) per the immune-related Response Evaluation Criteria in Solid Tumors irRECIST. (Phase I)

VI. Progression-free survival (PFS) rate at 1 year. (Phase I)

VII. Progression-free survival (PFS). (Phase I)

VIII. Overall survival (OS). (Phase I)

IX. Disease control rate (DCR) and stable disease (SD). (Phase I)

To evaluate the safety profile of Nimotuzaumab in combination with Nivolumab in NCSLC using the CTCAE V. 4.

TERTIARY OBJECTIVES:

Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and adverse events (AE). (Phase I)

III. Comparison of response assessment criteria for a prospective analysis; irRECIST response assessment; irRC. (Phase I)

IV. Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and AE. (Phase II)

Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels. (Phase II)

VI. Examine the relationship of PD-L1 expression within both neoplastic and non-neoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and AE. (Phase II)

VII. Comparison of response assessment criteria for a prospective analysis; irRECIST response assessment; irRC. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of nimotuzumab followed by a phase II study.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (nivolumab, nimotuzumab)	Experimental	Other: Laboratory Biomarker Analysis, Biological: Nimotuzumab, Biological: NivolumabPatients receive nivolumab IV over 60 minutes and nimotuzumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
Patients with pathologically confirmed non-small cell lung cancer
Patients must have had progressive NSCLC after first-line platinum-based chemotherapy for advanced disease
Have at least 3 months life expectancy
Have measurable disease per RECIST 1.1 criteria present

Key exclusion criteria (18 listed)

Active autoimmune disease that has required systemic treatment in past 2 years; use of inhaled corticosteroids is allowed
Phase II only: history of other malignancies are allowed as long as the current disease stage that did not require active treatment with concomitant systemic cytotoxic chemotherapy, targeted therapy, investigational or biologic therapy (e.g., anti-CTLA4 or HER2 monoclonal antibodies) within 12 months prior to study registration and, is not likely to require systemic therapy in the next 12 months; hormone-related therapies (e.g., somatostatin analogues, etc.) are allowed on a case-to-case basis upon discussion with principal investigator
Active clinically serious infections requiring antibiotics, antiviral or antifungal agents
Symptomatic brain metastases; uncontrolled pleural effusion, seroperitoneum, or pericardial effusion
Has had any major surgery, chemotherapy, or radiotherapy within the previous 4 weeks; gamma knife radiosurgery for brain metastases within less than 2 weeks

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Laboratory Biomarker AnalysisCorrelative studies	Other	Treatment (nivolumab, nimotuzumab)
NimotuzumabAlso: Thera-CIM-hr3, TheraCim hR3, TheralocGiven IV	Biological	Treatment (nivolumab, nimotuzumab)
NivolumabAlso: BMS-936558, MDX-1106, NIVO, ONO-4538Given IV	Biological	Treatment (nivolumab, nimotuzumab)

Primary outcome

DLT as graded by NCI CTCAE version 4.0 (Phase I)
Time frame: Up to 28 days
No formal analyses of DLTs are planned. Participants who do not have a DLT and who do not complete a full cycle of treatment will be considered non-evaluable for DLT.
ORR defined as complete response (CR) + partial response (PR) divided by number of patients as assessed by RECIST version 1.1 (Phase II)
Time frame: Up to 3 years
Will be calculated as the number of patients with a confirmed complete or partial response divided by the total number of patients. The 95% confidence interval for ORR (CR + PR) will be presented based on the Wilson Score method as irRC response.

1 secondary outcome

Incidence of adverse events assessed by NCI CTCAE version 4.0 (Phase I and II)
Time frame: Up to 30 days after the last dose of study treatment

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.

Related trials for EGFR Gene Mutation

RecruitingPhase 1/2
A Study of VRN110755 in Patients With EGFR-Mutant Non-Small Cell Lung Cancer
EGFR-Mutant Non-Small Cell Lung Cancer
RecruitingPhase 3
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
PIK3CA Mutation, HER2- Negative Breast Cancer
RecruitingPhase 1/2
Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Solid Tumors
Active, not recruitingPhase 1
Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
EGFR-mutant Non-small Cell Lung Cancer
RecruitingPhase 3
A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Non-small Cell Lung Cancer, HER2 Mutation

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Grace Dy principal investigator

Roswell Park Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DLT as graded by NCI CTCAE version 4.0 (Phase I) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02947386.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.