A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)

NCT ID: NCT05067283

Last Updated: 2026-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

830 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-17

Study Completion Date

2030-02-25

Brief Summary

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This is a study evaluating the safety, pharmacokinetics, and efficacy of MK-1084 alone, and MK-1084 plus other combination therapies in participants with advanced solid tumors with identified kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation.

Detailed Description

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Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

Participants will receive daily oral escalating doses of up to 800 mg of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral dose

Arm 2

Participants will receive MK-1084 daily oral escalating dose of up to 800 mg plus pembrolizumab given as a 200 mg intravenous infusion once every 21-day cycle up to a total of 35 cycles (up to \~24 months). Treatment with MK-1084 will continue until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral dose

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion of 200 mg

Arm 3

Participants will receive alternate formulation of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral dose

Arm 4

Participants will receive MK-1084 daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to \~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral dose

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous infusion of 200 mg

carboplatin

Intervention Type DRUG

Per label

pemetrexed

Intervention Type DRUG

Per label

Arm 5

Participants will receive MK-1084 daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral dose

cetuximab

Intervention Type BIOLOGICAL

Per label

Arm 6

Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral dose

cetuximab

Intervention Type BIOLOGICAL

Per label

oxaliplatin

Intervention Type DRUG

Per label

leucovorin

Intervention Type DRUG

Per label

5-fluorouracil

Intervention Type DRUG

Per label

Interventions

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MK-1084

Oral dose

Intervention Type DRUG

Pembrolizumab

Intravenous infusion of 200 mg

Intervention Type BIOLOGICAL

carboplatin

Per label

Intervention Type DRUG

pemetrexed

Per label

Intervention Type DRUG

cetuximab

Per label

Intervention Type BIOLOGICAL

oxaliplatin

Per label

Intervention Type DRUG

leucovorin

Per label

Intervention Type DRUG

5-fluorouracil

Per label

Intervention Type DRUG

Other Intervention Names

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KEYTRUDA® MK-3475

Eligibility Criteria

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Inclusion Criteria

For all participants:

* Has measurable disease by RECIST 1.1 criteria
* Has adequate organ function
* Male participants agree to protocol-specified contraception requirements including refraining from donating sperm and using protocol-specified contraceptives unless confirmed to be azoospermic
* Female participants must not be pregnant or breastfeeding, and must agree to protocol-specified contraceptive requirements and must have a negative highly sensitive pregnancy test within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention

For Arm 1 - Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically OR blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease

For Arm 2

\- Has an untreated metastatic non-small cell lung cancer (NSCLC) with histologically OR blood-based confirmation of KRAS G12C mutation and histologic confirmation of programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%

For Arm 3

* Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically or blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease Expansion Group A: 2L+NSCLC
* Has histologically or cytologically confirmed diagnosis of unresectable or metastatic NSCLC with histological or blood-based confirmation of KRAS G12C mutation and submits archival tumor sample
* Previous treatment failure of at least 1 line of systemic therapy Expansion Group B
* Has locally advanced unresectable or metastatic solid-tumor malignancy, excluding NSCLC or CRC, with histologically or blood- based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease

Arm 4 only - Has an untreated advanced or metastatic nonsquamous NSCLC with histologically or blood-based confirmation of KRAS G12C mutation

Arm 5 only

* Histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic colorectal adenocarcinoma and with histologically or blood-based confirmation of KRAS G12C mutation
* Previous treatment failure of one or 2 previous line(s) of systemic therapy

Arm 6 only

\- Locally advanced unresectable or metastatic colorectal adenocarcinoma with histologically or blood-based confirmation of KRAS G12C mutation

Exclusion Criteria

* Has received chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before first dose of study intervention
* Has a history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 5 years
* Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active infection requiring systemic therapy
* Known history of HIV infection or. has a known history of Hepatitis B virus or known active Hepatitis C virus infection
* Has a history of interstitial lung disease, noninfectious pneumonitis requiring active steroid therapy, or ongoing pneumonitis
* Has an active autoimmune disease requiring systemic therapy
* Has not fully recovered from any effects of major surgical procedure without significant detectable infection
* Has one or more of the following ophthalmological findings/conditions: intraocular pressure \>21 mm Hg and/or any diagnosis of glaucoma; diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and/or a diagnosis of retinal degenerative disease
* Has received live or live-attenuated vaccine within 4 weeks of study start

Arm 4 Only

* Is unable to interrupt aspirin or other nonsteroidal anti-inflammatories (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents \[for example, piroxicam\]) before, during, and for at least 2 days after administration of pemetrexed.
* Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Moffitt Cancer Center ( Site 0261)

Tampa, Florida, United States

Site Status RECRUITING

START Midwest ( Site 0267)

Grand Rapids, Michigan, United States

Site Status RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)

Hackensack, New Jersey, United States

Site Status RECRUITING

Laura and Isaac Perlmutter Cancer Center ( Site 0270)

New York, New York, United States

Site Status COMPLETED

NEXT Virginia ( Site 0271)

Fairfax, Virginia, United States

Site Status RECRUITING

MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0438)

La Rioja, , Argentina

Site Status RECRUITING

Chris O'Brien Lifehouse ( Site 0002)

Camperdown, New South Wales, Australia

Site Status RECRUITING

Liverpool Hospital-Medical Oncology ( Site 0001)

Liverpool, New South Wales, Australia

Site Status RECRUITING

Westmead Hospital ( Site 0006)

Westmead, New South Wales, Australia

Site Status RECRUITING

Monash Health-Oncology Research ( Site 0003)

Clayton, Victoria, Australia

Site Status RECRUITING

Cross Cancer Institute ( Site 0033)

Edmonton, Alberta, Canada

Site Status RECRUITING

The Moncton Hospital ( Site 0037)

Moncton, New Brunswick, Canada

Site Status RECRUITING

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0030)

Hamilton, Ontario, Canada

Site Status RECRUITING

Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 0036)

Kingston, Ontario, Canada

Site Status RECRUITING

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)

Toronto, Ontario, Canada

Site Status RECRUITING

Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0041)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

FALP-UIDO ( Site 0040)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Bradfordhill ( Site 0042)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

James Lind Centro de Investigacion del Cancer ( Site 0043)

Temuco, Región de la Araucanía, Chile

Site Status COMPLETED

Beijing Friendship Hospital Affiliate of Capital University-Oncology ( Site 0417)

Beijing, Beijing Municipality, China

Site Status RECRUITING

Fujian Cancer Hospital ( Site 0419)

Fuzhou, Fujian, China

Site Status RECRUITING

Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 0413)

Guangzhou, Guangdong, China

Site Status RECRUITING

Sun Yat-sen University Cancer Center-Internal medicine ( Site 0415)

Guangzhou, Guangdong, China

Site Status RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0418)

Wuhan, Hubei, China

Site Status RECRUITING

Jilin Cancer Hospital-oncology department ( Site 0412)

Changchun, Jilin, China

Site Status COMPLETED

Shanghai Chest Hospital-Oncology department ( Site 0410)

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanghai East Hospital ( Site 0416)

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Zhejiang Cancer Hospital-Thoracic oncology ( Site 0411)

Hangzhou, Zhejiang, China

Site Status RECRUITING

Odense Universitetshospital-Department of oncology ( Site 0421)

Odense, Region Syddanmark, Denmark

Site Status RECRUITING

Rambam Health Care Campus-Oncology ( Site 0090)

Haifa, , Israel

Site Status RECRUITING

Shaare Zedek Medical Center-Oncology ( Site 0092)

Jerusalem, , Israel

Site Status RECRUITING

Hadassah Medical Center-Oncology ( Site 0094)

Jerusalem, , Israel

Site Status RECRUITING

Meir Medical Center. ( Site 0091)

Kfar Saba, , Israel

Site Status RECRUITING

Sheba Medical Center-ONCOLOGY ( Site 0093)

Ramat Gan, , Israel

Site Status RECRUITING

Humanitas ( Site 0113)

Rozzano, Lombardy, Italy

Site Status RECRUITING

ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0111)

Siena, Tuscany, Italy

Site Status RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0110)

Napoli, , Italy

Site Status RECRUITING

National Cancer Center Hospital East ( Site 0404)

Kashiwa, Chiba, Japan

Site Status RECRUITING

Kanagawa Cancer Center ( Site 0402)

Yokohama, Kanagawa, Japan

Site Status RECRUITING

Shizuoka Cancer Center ( Site 0401)

Nakatogari, Shizuoka, Japan

Site Status RECRUITING

National Cancer Center Hospital ( Site 0403)

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

Cancer Institute Hospital of JFCR ( Site 0400)

Koto, Tokyo, Japan

Site Status RECRUITING

Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 0121)

Kaunas, Kaunas County, Lithuania

Site Status RECRUITING

Vilnius University Hospital Santaros Clinics Affiliate - National Cancer Center ( Site 0120)

Vilnius, , Lithuania

Site Status RECRUITING

Sarawak General Hospital ( Site 0453)

Kuching, Sarawak, Malaysia

Site Status RECRUITING

New Zealand Clinical Research (Christchurch) ( Site 0004)

Christchurch, Canterbury, New Zealand

Site Status COMPLETED

Centro Oncologico de Panama ( Site 0160)

Panama City, , Panama

Site Status RECRUITING

Centro Hemato Oncológico Paitilla ( Site 0163)

Panama City, , Panama

Site Status COMPLETED

Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0172)

Poznan, Greater Poland Voivodeship, Poland

Site Status RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0170)

Warsaw, Masovian Voivodeship, Poland

Site Status RECRUITING

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0171)

Gdansk, Pomeranian Voivodeship, Poland

Site Status RECRUITING

Oddzial Onkologii Klinicznej z Pododdzialem Chemioterapii Jednodniowej ( Site 0173)

Koszalin, West Pomeranian Voivodeship, Poland

Site Status RECRUITING

Seoul National University Hospital ( Site 0191)

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center-Division of Hematology/Oncology ( Site 0193)

Seoul, , South Korea

Site Status RECRUITING

Clinica Universidad de Navarra ( Site 0213)

Madrid, Madrid, Comunidad de, Spain

Site Status RECRUITING

Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0211)

Madrid, Madrid, Comunidad de, Spain

Site Status RECRUITING

Hospital Universitari Vall d'Hebron-Oncology ( Site 0212)

Barcelona, , Spain

Site Status RECRUITING

Cantonal Hospital St.Gallen ( Site 0224)

Sankt Gallen, Canton of St. Gallen, Switzerland

Site Status RECRUITING

Ospedale Regionale Bellinzona e Valli ( Site 0220)

Bellinzona, Canton Ticino, Switzerland

Site Status RECRUITING

Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 0445)

Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital ( Site 0444)

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital-Oncology ( Site 0443)

Taipei, , Taiwan

Site Status RECRUITING

Ege University Medicine of Faculty ( Site 0231)

Bornova, İzmir, Turkey (Türkiye)

Site Status COMPLETED

Erciyes University ( Site 0232)

Talas, Kayseri, Turkey (Türkiye)

Site Status COMPLETED

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0234)

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Ankara City Hospital-oncology ( Site 0233)

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 0254)

Cherkasy, Cherkasy Oblast, Ukraine

Site Status RECRUITING

Communal Non-Commercial Enterprise Prykarpatski Clinical Onc-Chemotherapy department ( Site 0251)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Site Status RECRUITING

Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Site 0255)

Kropyvnytskyi, Kirovohrad Oblast, Ukraine

Site Status RECRUITING

Rivne Regional Clinical Hospital ( Site 0257)

Rivne, Rivne Oblast, Ukraine

Site Status COMPLETED

ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0259)

Rivne, Rivne Oblast, Ukraine

Site Status RECRUITING

Uzhhorod Multispecialty City Clinical Hospital ( Site 0258)

Uzhhorod, Zakarpattia Oblast, Ukraine

Site Status RECRUITING

Countries

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United States Argentina Australia Canada Chile China Denmark Israel Italy Japan Lithuania Malaysia New Zealand Panama Poland South Korea Spain Switzerland Taiwan Turkey (Türkiye) Ukraine

Central Contacts

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Toll Free Number

Role: CONTACT

1-888-577-8839

Facility Contacts

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Study Coordinator

Role: primary

813-745-5995

Study Coordinator

Role: primary

616-954-5554

Study Coordinator

Role: primary

551-996-5900

Study Coordinator

Role: primary

703-280-5390

Study Coordinator

Role: primary

414-805-0505

Study Coordinator

Role: primary

+549380 4425438

Study Coordinator

Role: primary

61285140162

Study Coordinator

Role: primary

61287389744

Study Coordinator

Role: primary

+61403170371

Study Coordinator

Role: primary

6385722429

Study Coordinator

Role: primary

780-908-8213

Study Coordinator

Role: primary

506-857-5104

Study Coordinator

Role: primary

905-387-9495

Study Coordinator

Role: primary

613-549-6666x4502

Study Coordinator

Role: primary

416-946-4501

Study Coordinator

Role: primary

+56 9 9161 2199

Study Coordinator

Role: primary

+56981369487

Study Coordinator

Role: primary

+56998744662

Study Coordinator

Role: primary

01063138585

Study Coordinator

Role: primary

0591-62752500

Study Coordinator

Role: primary

8620 62787110

Study Coordinator

Role: primary

86 02087343801

Study Coordinator

Role: primary

027-85726685

Study Coordinator

Role: primary

021-22200000

Study Coordinator

Role: primary

1-888-577-8839

Study Coordinator

Role: primary

0571-88122092

Study Coordinator

Role: primary

+45 66113333

Study Coordinator

Role: primary

+97247776234

Study Coordinator

Role: primary

+97226555768

Study Coordinator

Role: primary

+97226776760

Study Coordinator

Role: primary

97297472414

Study Coordinator

Role: primary

+97235304498

Study Coordinator

Role: primary

00390282244559

Study Coordinator

Role: primary

00390577586335

Study Coordinator

Role: primary

08117770810

Study Coordinator

Role: primary

+81-4-7133-1111

Study Coordinator

Role: primary

+81-45-520-2222

Study Coordinator

Role: primary

+81-55-989-5222

Study Coordinator

Role: primary

+81-3-3542-2511

Study Coordinator

Role: primary

+81-3-3520-0111

Study Coordinator

Role: primary

+370 600 04799

Study Coordinator

Role: primary

+37064565101

Study Coordinator

Role: primary

082-276666

Study Coordinator

Role: primary

+50764807461

Study Coordinator

Role: primary

48606228277

Study Coordinator

Role: primary

48225463381

Study Coordinator

Role: primary

48585844571

Study Coordinator

Role: primary

+48 94 348 84 00

Study Coordinator

Role: primary

82220722995

Study Coordinator

Role: primary

+82-2-3410-3459

Study Coordinator

Role: primary

34913531920x7501

Study Coordinator

Role: primary

34 91 550 48 00x2689

Study Coordinator

Role: primary

34 93 274 60 00x6988

Study Coordinator

Role: primary

071/494 11 11

Study Coordinator

Role: primary

41918118045

Study Coordinator

Role: primary

886-7-7317123

Study Coordinator

Role: primary

+88662353535

Study Coordinator

Role: primary

+886223123456

Study Coordinator

Role: primary

905334318506

Study Coordinator

Role: primary

+90 312 552 60 00

Study Coordinator

Role: primary

+380472370123

Study Coordinator

Role: primary

+380502094000

Study Coordinator

Role: primary

+380522366001

Study Coordinator

Role: primary

+380503802915

Study Coordinator

Role: primary

+380312642332

References

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Ma X, Sloman DL, Duggal R, Anderson KD, Ballard JE, Bharathan I, Brynczka C, Gathiaka S, Henderson TJ, Lyons TW, Miller R, Munsell EV, Orth P, Otte RD, Palani A, Rankic DA, Robinson MR, Sather AC, Solban N, Song XS, Wen X, Xu Z, Yang Y, Yang R, Day PJ, Stoeck A, Bennett DJ, Han Y. Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRASG12C Inhibitor. J Med Chem. 2024 Jul 11;67(13):11024-11052. doi: 10.1021/acs.jmedchem.4c00572. Epub 2024 Jun 26.

Reference Type DERIVED
PMID: 38924388 (View on PubMed)

Related Links

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Other Identifiers

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MK-1084-001

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2041220034

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-501563-40-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1281-2482

Identifier Type: REGISTRY

Identifier Source: secondary_id

1084-001

Identifier Type: -

Identifier Source: org_study_id

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