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HCCPhase 2NCT04988945

TACE and SBRT Followed by Double Immunotherapy for Downstaging Hepatocellular Carcinoma

A Phase 2 study testing TACE, SBRT and Durvalumab in people with HCC, run by The University of Hong Kong at 2 sites in Hong Kong.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study is a prospective phase II, single arm mono-institutional study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of the sequential administration of trans-arterial chemo-embolization (TACE) and stereotactic body radiotherapy (SBRT) with immune checkpoint inhibitors in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HCC
What is being tested?
TACE, SBRT and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
2 sitesHong Kong
Study dates
1 Dec 2020to 31 Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • For inclusion in the study, patients should fulfill the following criteria:
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
  • Diagnosis of unresectable HCC confirmed pathologically or made according to
  • American Association for the Study of Liver Diseases (AASLD) practice guideline 2010:
  • patients with cirrhosis of any etiology and patients with chronic hepatitis B (HBV) who may not have fully developed cirrhosis, the presence of liver nodule >1cm and demonstrated in a single contrast-enhanced dynamic imaging [either computed tomography (CT) or magnetic resonance imaging (MRI)] of intense arterial uptake and "washout" in portal venous and delayed phases.
  • Adult male or female aged >18 years at time of study entry
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  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Body weight >30kg
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Must have a life expectancy of at least 12 weeks
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Tumor size 5-25cm and number of lesions ≤3
  • Portal vein involvement (Vp1-3) is allowed: Vp1, presence of a tumor thrombus distal to, but not within, the second-order branches of the portal vein; Vp2, presence of a tumor thrombus in the second-order branches of the portal vein; Vp3, presence of a tumor thrombus in the first-order branches of the portal vein.
  • Liver volume minus gross tumor volume (GTV) > 700cc
  • Child-Pugh liver function class A-B7
  • No prior immunotherapy
  • Subjects with confirmed concomitant HBV infection (defined as HBsAg positive or HBV DNA detectable) that are eligible for inclusion must be treated with antiviral therapy (per local institutional practice) prior to enrollment to ensure adequate viral suppression (HBV DNA < 2000 IU/mL), must remain on antiviral therapy for the study duration, and continue therapy for 6 months after the last dose of investigational product(s)
  • At least one measurable lesion according to RECIST v1.1.
  • Adequate normal organ and marrow function as defined below:
  • Haemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC ≥1.5 (or 1.0) x (> 1500 per mm^3)
  • Platelet count ≥ 75 x 109/L (>75,000 per mm^3)
  • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
  • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
  • Measured creatinine clearance (CL) >45 mL/min or Calculated creatinine clearance CL>45 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

Who cannot join

  • Patients should not enter the study if any of the following exclusion criteria are fulfilled:
  • Participation in another clinical study with an investigational product within 4 weeks prior to the first dose of study treatment
  • Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with Durvalumab or Tremelimumab may be included only after consultation with the Study Physician.
Show all 50Show fewer
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
  • Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Prior radiotherapy to the region of liver or selective internal radiotherapy
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • History of primary immunodeficiency or allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
  • History of another primary malignancy except for
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • History of leptomeningeal carcinomatosis
  • Presence of extra-hepatic metastases (M1). Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
  • Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (RECIST)) for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF.
  • History of active primary immunodeficiency
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of Durvalumab or Tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
  • Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of Durvalumab monotherapy or180 days after the last dose of Durvalumab + Tremelimumab combination therapy.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Prior randomisation or treatment in a previous Durvalumab and/or Tremelimumab clinical study regardless of treatment arm assignment.
  • Patients who have received prior anti-PD-1, anti-PD-L1 or anti-CTLA-4:
  • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
  • All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
  • Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
  • Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.
  • Contraindicated of SBRT:
  • Any one hepatocellular carcinoma > 25 cm
  • Total maximal sum of hepatocellular carcinoma > 30 cm
  • More than 3 discrete hepatic nodule
  • Direct tumor extension into the stomach, duodenum, small bowel, large bowel, common or main branch of biliary tree
  • Main portal vein, contralateral portal vein, (Vp4) or inferior vena cava (IVC) thrombosis / involvement
  • Presence of clinically meaningful ascites as ascites requiring non pharmacologic intervention (eg, paracentesis) or escalation in pharmacologic intervention to maintain symptomatic control
  • Hepatic encephalopathy
  • Active or prior documented gastrointestinal variceal bleeding

Trial locations and contacts

2 sites in 1 country.

Hong Kong2 sites

  • Department of Surgery, The University of Hong Kong

    Hong Kong

  • The University of Hong Kong

    Hong Kong

Other trials in Hong Kong

About this study

Official title: Sequential TransArterial Chemoembolization and Stereotactic RadioTherapy Followed by Durvalumab (MEDI4736) and Tremelimumab for Downstaging Hepatocellular Carcinoma for Hepatectomy

This study is a prospective phase II, single arm mono-institutional study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of the sequential administration of trans-arterial chemo-embolization (TACE) and stereotactic body radiotherapy (SBRT) with immune checkpoint inhibitors in unresectable hepatocellular carcinoma (HCC) patients.

Read the detailed description

Hepatocellular carcinoma (HCC) is a serious global health problem. It ranks the fifth in incidence and third in cancer-related mortality at Hong Kong in 2015. The disease has high mortality rate, and surgery is the only curative therapy although only 30% of patients are diagnosed early enough to undergo liver resection or transplantation or radiofrequency ablation (RFA). For inoperable patients with disease limited to liver, trans-arterial chemo-embolization (TACE) is the most commonly used therapy. Previous randomized studies have demonstrated its survival benefit, however it rarely cures the disease; also its efficacy is very limited in patients with sizable tumor or multi-focal diseases. Efforts have been made to improve the response of treatment, but none has consistently demonstrated the benefit. As a result, over the past decade, there is no major advancement in the treatment strategy for intermediate stage HCC patients. Recently, stereotactic body radiotherapy (SBRT) has emerged as one of the promising local therapy of HCC. This advanced radiotherapy technique allows killing of cancer cells by delivering a potent dose of radiation with excellent geometric precision. Data have demonstrated its favorable local control rate and toxicity profile in locally advanced HCC. Further, recent studies, including our series, indicated that combining SBRT and TACE is therapeutically superior. As such, it is postulated that combined TACE+SBRT is a more potent local therapy than TACE in preventing tumor progression, and it may potentially translate into survival benefit.

The recent discovery in immune-oncology represents another breakthrough in management of HCC. Pre-clinical data showed that there is high expression of immunosuppressive cells and up-regulation of programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immune checkpoints in the HCC microenvironment; it provides the rationale for immunotherapy to be used in this setting. This premise was supported by several early phase clinical studies, in which anti-PD-1/programmed death ligand 1 (PD-L1) therapy resulted in a durable response and favorable survival. More intriguingly, there are scientific and clinical data in supporting the synergy between immune checkpoint inhibitors (ICI) and SBRT for both local tumor regression and distant control (out-of-the-field abscopal) effect. For high risk HCC, such approach may warrant further exploration.

Based on all these, a hypothesis is made that combined TACE+SBRT followed by immunotherapy is a promising strategy in treating unresectable HCC. In this single-arm prospective phase II study, it is aimed at evaluating the efficacy and safety of this treatment regime.

Conditions
HCC
Keywords
HCC, TACE, SBRT, immunotherapy, hepatocellular carcinoma, liver cancer, unresectable, large liver tumour
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

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

  • TACEProcedure or surgery

    Procedure of TACE will be standardized.

  • SBRTRadiation

    SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.

  • DurvalumabDrug

    1500mg Durvalumab administered IV over 60 minutes on Day 1 of each immunotherapy treatment every 4 weeks until disease progression (PD)

  • TremelimumabDrug

    300mg Tremelimumab administered over 60 minutes on Day 1 of cycle 1.

Study groups in NCT04988945
Study groupRoleWhat they receive
Durvalumab + TremelimumabExperimental1500mg Durvalumab administered IV over 60 minutes on Day 1 of each immunotherapy treatment every 4 weeks until disease progression (PD) and 300mg Tremelimumab administered over 60 minutes on Day 1 of cycle 1.
Receives: Procedure: TACE; Radiation: SBRT; Drug: Durvalumab; Drug: Tremelimumab

What is being measured

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

  1. Downstaging for hepatectomy

    To assess the number of patients amendable to curative surgical interventions (resection or radiofrequency ablation) after successful down-sizing of tumor(s) by intervention in HCC patients treated with combined TACE and SBRT followed by Durvalumab plus Tremelimumab

    Measured: From the date of first study treatment to the date of last study treatment, an average of 3 years

Secondary outcomes (7)

  1. Response rate measured by mRECIST criteria

    Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started

    Measured: From the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years

  2. Time to progression (TTP)

    measured from the date of first study treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.

    Measured: From the date of first study treatment to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years

  3. Progression-free survival (PFS)

    measured from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.

    Measured: From the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years

  4. Overall survival (OS)

    measured from date of first study treatment to the date of death from any cause

    Measured: From the date of first study treatment to the date of death from any cause, assessed up to 5 years

  5. Toxicity tolerability measurement in treatment related procedure

    To measure the toxicities in HCC patients treated with combined TACE and SBRT followed by Durvalumab plus Tremelimumab. Dosage used will be recorded each time together with the response of patients. If any adverse event happens, the highest dosage will be noted down.

    Measured: From the date of screening to 90 days after last treatment, around 3 years and 90 days

  6. Questionnaire based Quality of Life (QoL) assessment

    To evaluate the patient-reported quality of life (QoL) treated with combined TACE and SBRT followed by Durvalumab plus Tremelimumab. Questionnaires EORTC-QLQ-C30 and FACT Hep will be used

    Measured: From the date of screening to radiographically documented progression according to mRECIST 1.1, an average of 3 years

  7. Pathological response

    Defined as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used. Pathological complete response (pCR) is defined by the absence of viable tumor cells in any nodule.

    Measured: From the date of first study treatment to amendable to surgery after receiving combined TACE and SBRT followed by Durvalumab plus Tremelimumab, whichever occurs first, assessed up to 5 years

Timeline

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

  1. First posted4 Aug 2021
  2. Study start1 Dec 2020
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04988945
Sponsor's protocol ID
UW 20-046
Status last verified
Sep 2026
First submitted
29 Jun 2021
Last updated
25 Sep 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006 Apr 15;106(8):1653-63. doi: 10.1002/cncr.21811.

    PubMed 16541431

  • Seong J, Kim SH, Suh CO. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma. J Gastroenterol Hepatol. 2001 Aug;16(8):883-9. doi: 10.1046/j.1440-1746.2001.02533.x.

    PubMed 11555102

  • Chiang CL, Chan MKH, Yeung CSY, Ho CHM, Lee FAS, Lee VWY, Wong FCS, Blanck O. Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B-C hepatocellular carcinoma. Strahlenther Onkol. 2019 Mar;195(3):254-264. doi: 10.1007/s00066-018-1391-2. Epub 2018 Nov 9.

    PubMed 30413833

  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.

    PubMed 22437870

  • Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008 Aug;224:166-82. doi: 10.1111/j.1600-065X.2008.00662.x.

    PubMed 18759926

  • Stewart R, Morrow M, Hammond SA, Mulgrew K, Marcus D, Poon E, Watkins A, Mullins S, Chodorge M, Andrews J, Bannister D, Dick E, Crawford N, Parmentier J, Alimzhanov M, Babcook JS, Foltz IN, Buchanan A, Bedian V, Wilkinson RW, McCourt M. Identification and Characterization of MEDI4736, an Antagonistic Anti-PD-L1 Monoclonal Antibody. Cancer Immunol Res. 2015 Sep;3(9):1052-62. doi: 10.1158/2326-6066.CIR-14-0191. Epub 2015 May 5.

    PubMed 25943534

  • Tarhini AA, Kirkwood JM. Tremelimumab (CP-675,206): a fully human anticytotoxic T lymphocyte-associated antigen 4 monoclonal antibody for treatment of patients with advanced cancers. Expert Opin Biol Ther. 2008 Oct;8(10):1583-93. doi: 10.1517/14712598.8.10.1583.

    PubMed 18774925

  • Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2015 Jun 10;33(17):1889-94. doi: 10.1200/JCO.2014.56.2736. Epub 2015 Feb 9.

    PubMed 25667295

  • Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jul 11;369(2):122-33. doi: 10.1056/NEJMoa1302369. Epub 2013 Jun 2.

    PubMed 23724867

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TACE, SBRT and Durvalumab in people with HCC, run by The University of Hong Kong at 2 sites in Hong Kong.

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 27 inclusion and 50 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: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Hong Kong. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Downstaging for hepatectomy (time frame: From the date of first study treatment to the date of last study treatment, an average of 3 years). 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 NCT04988945, which also lists 9 linked publications.

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 25 Sep 2026.

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