AZD0901 u účastníků s pokročilými solidními nádory exprimujícími Claudin18.2
Otevřená multicentrická studie fáze II k hodnocení bezpečnosti, snášenlivosti, účinnosti, farmakokinetiky a imunogenicity AZD0901 jako monoterapie a v kombinaci s protirakovinnými látkami u účastníků s pokročilými solidními nádory exprimujícími Claudin 18.2.
The purpose of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and immunogenicity of AZD0901 as monotherapy and in combination with anti-cancer agents in participants with locally advanced unresectable or metastatic solid tumours expressing CLDN18.2 .
Přehled studie
Postavení
Podmínky
Detailní popis
This open-label, multi-centre study consists of individual sub studies, each evaluating the safety and tolerability of AZD0901.
Sub study 1 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic gastric esophageal cancer expressing CLDN18.2. Participants will receive AZD0901 monotherapy via intravenous (IV) infusion and will be randomised in to one of 2 arms.
Sub study 2 will consist of two parts, a safety run-in and a dose expansion part to investigate the safety and efficacy of AZD0901 in combination with different chemotherapy agents in participants with pancreatic cancer. Substudy 3 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic Biliary tract cancer.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: AstraZeneca Clinical Study Information Center
- Telefonní číslo: 1-877-240-9479
- E-mail: information.center@astrazeneca.com
Studijní místa
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Melbourne, Austrálie, 3000
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Murdoch, Austrálie, WA6150
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Randwick, Austrálie, 2031
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Tbilisi, Gruzie, 0112
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Chūōku, Japonsko, 104-0045
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Kashiwa, Japonsko, 227-8577
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Kitaadachi-gun, Japonsko, 362-0806
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Kōtoku, Japonsko, 135-8550
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Nagoya, Japonsko, 464-8681
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Osakasayama-shi, Japonsko, 589-8511
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Gyeonggi-do, Jižní Korea, 13620
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Seoul, Jižní Korea, 03080
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Seoul, Jižní Korea, 06351
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Seoul, Jižní Korea, 05505
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Seoul, Jižní Korea, 03722
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Ontario
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Kingston, Ontario, Kanada, K7L 2V7
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Toronto, Ontario, Kanada, M5G 2M9
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Quebec
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Montreal, Quebec, Kanada, H3G 1A4
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Sherbrooke, Quebec, Kanada, J1G 2E8
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George Town, Malajsie, 10450
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Johor Bahru, Malajsie, 81100
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Kuala Lumpur, Malajsie, 59100
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Kuala Selangor, Malajsie, 62250
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Kuching, Malajsie, 93586
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Chisinau, Moldavsko, MD-2025
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Krakow, Polsko, 31-501
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Warsaw, Polsko, 02-034
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Bukit Merah, Singapur, 169610
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Singapore, Singapur, 308433
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Singapore, Singapur, 119074
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Singapore, Singapur, 329563
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Glasgow, Spojené království, G12 0YN
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Leeds, Spojené království, LS9 7TF
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London, Spojené království, NW3 2QG
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Oxford, Spojené království, OX3 7LE
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California
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Orange, California, Spojené státy, 92868
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Palo Alto, California, Spojené státy, 94304
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Santa Rosa, California, Spojené státy, 95403
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Kentucky
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Louisville, Kentucky, Spojené státy, 40202
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New York
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Commack, New York, Spojené státy, 11725
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Rhode Island
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Providence, Rhode Island, Spojené státy, 02903
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Texas
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Houston, Texas, Spojené státy, 77030
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Kaohsiung City, Tchaj-wan, 80756
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Taichung, Tchaj-wan, 404
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Tainan, Tchaj-wan, 70403
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Taipei, Tchaj-wan, 11217
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Taoyuan, Tchaj-wan, 00333
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Changsha, Čína, 410013
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Chengdu, Čína, 610041
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Barcelona, Španělsko, 08035
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Madrid, Španělsko, 28007
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Madrid, Španělsko, 28040
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
The list below is a summarised eligibility criteria for the study - refer to the study protocol for full criteria.
Master Inclusion Criteria applicable to all sub studies:
- Participant must be ≥ 18 years or the legal age of consent at the time of signing the ICF.
- Participants who are CLDN18.2 positive.
- Must have at least one measurable lesion according to RECIST v1.1.
- ECOG performance status of 0 to 1 with no deterioration over the previous 2 weeks prior first day of dosing.
- Predicted life expectancy of ≥ 12 weeks.
- Adequate organ and bone marrow function as defined by protocol.
- Body weight > 35 kg.
- Participants are willing to comply with contraception requirements.
Sub study 1 Specific Inclusion criteria:
- Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction.
- Advanced or metastatic GC/GEJC.
- Maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.
Sub study 2 Specific Inclusion criteria:
- Participants diagnosed with histologically confirmed metastatic or advanced PDAC.
- Availability of an archival sample or a fresh tumour biopsy taken at screening.
- No prior treatments for unresectable or metastatic disease. Prior neoadjuvant/adjuvant chemotherapy is permitted as long as participants progressed ≥ 6 months (183 days) from the last dose.
Sub study 3 Specific Inclusion criteria
- Histologically confirmed, unresectable advanced, or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma (NOTE: Ampullary cancers are not eligible).
- Documented radiographic or clinical disease progression on or after at least one prior regimen and maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.
Master Exclusion Criteria applicable to all sub studies:
- Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding in the setting of prior CLDN18.2 directed therapy.
- Participants with clinically significant ascites that require drainage.
- A history of drug-induced non-infectious ILD/pneumonitis.
- Central nervous system metastases or CNS pathology.
- Peripheral neuropathy, sensory, or motor ≥ Grade 2 at screening.
- History of another primary malignancy.
- Prior exposure to any MMAE-based ADC.
- Prior exposure to any CLDN18.2 targeted agents except anti-CLDN18.2 monoclonal antibody.
Sub study 1 Specific Exclusion criteria:
- Participants with HER2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC unless they have failed/not tolerated/or are not eligible for standard anti-HER2 therapy, where available.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
- The use of concomitant medications known to prolong the QT/QTc interval.
Sub study 2 Specific Exclusion criteria:
- Known DPD enzyme deficiency based on local testing where testing is SoC.
- Use of strong inhibitor or inducer of UGT1A1.
- Use of strong inhibitors or inducers of CYP3A4.
- Known homozygous for the UGT1A1*28 allele based on local testing where testing is SoC.
Sub study 3 Specific Exclusion criteria
• Clinically significant biliary obstruction that has not resolved before enrollment.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Sub Study 1 - AZD0901 MONOTHERAPY
Sub Study 1 will investigate AZD0901 monotherapy in order to evaluate the safety, tolerability, and efficacy of AZD0901. |
Antibody-drug conjugate/Biologic
Ostatní jména:
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Experimentální: Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents |
Antibody-drug conjugate/Biologic
Ostatní jména:
Chemotherapy agents
Ostatní jména:
Chemotherapy agents
Ostatní jména:
Chemotherapy agents
Ostatní jména:
Chemotherapy agents
Ostatní jména:
Chemotherapy agents
Ostatní jména:
Chemotherapy agents
Ostatní jména:
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Experimentální: Sub Study 3: AZD0901 MONOTHERAPY IN BILIARY TRACT CANCER
Substudy 3 Further evaluate the preliminary anti-tumour activity of AZD0901 monotherapy by assessment of DRR. |
Antibody-drug conjugate/Biologic
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Incidence of adverse events (AEs), serious AEs (SAEs). Changes from baseline in clinical laboratory parameters, vital signs, ECGs and physical examination. Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs.
Časové okno: 30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
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To investigate the safety and tolerability, of AZD0901 monotherapy or in combination with anti-cancer agents in particpants with advanced or metastatic solid tumours expressing CLDN18.2. |
30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
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Objective Response Rate (ORR).
Časové okno: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
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Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) as determined by the Investigator at local site as per RECIST v1.1. |
From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Overall Survival (OS)
Časové okno: From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).
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The analysis will include all dosed/randomised participants as assigned/randomised. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. |
From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).
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Progression Free Survival (PFS)
Časové okno: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
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Progression-free survival is defined as the time date of randomisation or enrollment until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause, regardless of whether the participant withdraws from randomized therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST v1.1 progression. |
From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
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Duration of Response (DoR)
Časové okno: From the date of first documented confirmed response until date of documented progression (approximately 2 years).
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The time from the date of first documented confirmed response until date of first documented progression per RECIST v1.1 or death due to any cause. |
From the date of first documented confirmed response until date of documented progression (approximately 2 years).
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Disease control rate (DCR)
Časové okno: Up to 11 weeks post date of first dose/randomisation
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The percentage of participants who have a confirmed CR or PR or who have SD per RECIST v1.1 as assessed by the Investigator at local site and derived from the raw tumour data up to 11 weeks after date of first dose/randomisation. |
Up to 11 weeks post date of first dose/randomisation
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Percentage change in tumor size
Časové okno: From start through to study completion.
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The best percentage change from baseline in tumor size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST v1.1 assessments. |
From start through to study completion.
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Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE
Časové okno: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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To characterise the PK of AZD0901 monotherapy or in combination with anti cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2. |
From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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Serum PK parameters of AZD0901, total antibody (conjugated and unconjugated) and MMAE including but not limited to AUC, Cmax, tmax, clearance and half-life, as data allow.
Časové okno: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
|
To characterise the PK of AZD0901 monotherapy or in combination with anti cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2. |
From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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Clinical activity by baseline and/or on-treatment tissue-based biomarkers including, but not limited to, gene expression, mutation profiles, DNA damage, protein expression, immune response and/or mechanisms of resistance.
Časové okno: From date of first dose of AZD0901 up to 7 weeks.
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To investigate baseline and/or on-treatment tissue-based RNA, DNA, and/or proteins, and association with clinical activity of AZD0901 (substudy 1). |
From date of first dose of AZD0901 up to 7 weeks.
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ADA status will be determined along with prevalence and incidence of anti-drug antibodies to AZD0901, and titer established.
Časové okno: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
|
To determine the immunogenicity of AZD0901 monotherapy or in combination with anti-cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2. |
From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Novotvary podle místa
- Novotvary
- Gastrointestinální novotvary
- Novotvary trávicího systému
- Nemoci trávicího systému
- Gastrointestinální onemocnění
- Onemocnění žaludku
- Nemoci žlučových cest
- Novotvary žaludku
- Novotvary žlučových cest
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Camptothecin
- Alkaloidy
- Enzymy a koenzymy
- Deoxycytidin
- Cytidin
- Pyrimidinové nukleosidy
- Pyrimidiny
- Formyltetrahydrofoláty
- Tetrahydrofoláty
- Kyselina listová
- Pteriny
- Pteridiny
- Uracil
- Pyrimidinony
- Koenzymy
- Irinotekan
- Gemcitabin
- Fluorouracil
- Leukovorin
- irinotecan sucrosofate
Další identifikační čísla studie
- D9800C00001
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
Časový rámec sdílení IPD
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Kritéria přístupu pro sdílení IPD
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
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