AzTrials
AzTrials

Metastatic Colorectal CancerPhase 3NCT04456699

Efficacy and Safety of Olaparib (MK-7339) With or Without Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Unresectable or Metastatic Colorectal Cancer (CRC) (MK-7339-003/LYNK-003)

A Phase 3 study testing Olaparib, 5-FU and Bevacizumab in people with Metastatic Colorectal Cancer, run by Merck Sharp & Dohme LLC at 129 sites in 18 countries.

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 is an efficacy and safety study of olaparib alone or in combination with bevacizumab being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Olaparib, 5-FU and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
335 participants
Where
129 sitesin 18 countries
Study dates
19 Aug 2020to 6 Nov 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Has a histologically-confirmed metastatic or unresectable (Stage IV as defined by American Joint Committee on Cancer (AJCC eighth edition) colorectal adenocarcinoma (National Comprehensive Cancer Network [NCCN] 2018).
  • Has not progressed (ie, achieved a stable disease [SD], partial response [PR], or complete response [CR]) after a first-line induction course of at least 6 cycles of folinic acid/fluorouracil/oxaliplatin (FOLFOX) + bevacizumab or 4 cycles of capecitabine and oxaliplatin (CAPOX) + bevacizumab as first-line therapy.
  • Participants must not have received an investigational agent during their induction course.
  • Determination of best overall response (SD/PR/CR) will be made by the investigator.
  • Non-Progressive Disease (PD) will be verified by BICR prior to randomization based on the images submitted to imaging contract research organization (iCRO) as described in inclusion criterion 4.
  • "First-line therapy" is defined as the first systemic chemotherapy regimen given for the diagnosis of unresectable or metastatic colorectal cancer (CRC). Participants may have received prior adjuvant/neoadjuvant chemotherapy for CRC, as long as it was completed at least 6 months prior to initiation of first-line CAPOX + bevacizumab or FOLFOX + bevacizumab induction treatment.
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  • Has experienced unacceptable toxicity to oxaliplatin that, in the opinion of the treating physician, requires/required the discontinuation of oxaliplatin. Note: As an example, unacceptable toxicity may include (but is not limited to) severe or prolonged neurotoxicity.
  • Participants must be randomized within a minimum of 2 weeks and a maximum of 6 weeks after their last dose of CAPOX + bevacizumab or FOLFOX + bevacizumab (last dose is the day of the last infusion that contained oxaliplatin).
  • Has provided to the iCRO 1 set of baseline radiographic images taken before or during the CAPOX + bevacizumab or FOLFOX + bevacizumab induction period and at least 42 days prior to the imaging performed during Screening. Tumor imaging at Screening must be performed within 28 days prior to the date of randomization.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to randomization.

Who cannot join

  • Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU, capecitabine, or olaparib.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 28 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid intervention for at least 14 days prior to first dose of study intervention.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
  • Has a known history of or is positive for hepatitis B surface antigen (HBsAg reactive) or hepatitis C ribonucleic acid (HCV RNA [qualitative]) is detected). Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
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  • Has myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with features suggestive of MDS/AML.
  • Has hemoptysis or hematemesis within 28 days prior to randomization.
  • Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation).
  • Has clinically significant bleeding within 28 days prior to randomization.
  • Is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high-resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
  • Has 1 or more conditions that, in the opinion of the treating physician, make the participant ineligible for treatment with bevacizumab. These conditions may include:
  • Uncontrolled hypertension (systolic blood pressure [SBP] >150 mm Hg or diastolic blood pressure [DBP] >100 mm Hg) or a history of hypertensive crisis or hypertensive encephalopathy
  • Arterial thromboembolic events (eg, myocardial infarction, cerebral infarction)
  • History of nephrotic syndrome or moderate proteinuria
  • History of gastrointestinal perforation
  • History of non-gastrointestinal fistula formation
  • History of possible reversible encephalopathy syndrome (RPLS)
  • Has received prior systemic anticancer therapy (other than CAPOX + bevacizumab or FOLFOX + bevacizumab induction) including investigational agents within 28 days prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with persistent alopecia or Grade ≤3 neuropathy are eligible.
  • Has received prior therapy with olaparib or with any other polyadenosine 5'-diphosphoribose polymerase (PARP) inhibitor.
  • Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period prior to randomization is 2 weeks.
  • Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to randomization is 5 weeks for phenobarbital and 3 weeks for other agents.
  • Has undergone major surgery within 2 weeks of randomization or has not recovered adequately from toxicities and/or complications from any major surgery prior to randomization.

Trial locations and contacts

129 sites in 18 countries.

129 sites in 18 countries

United States23 sites

  • University Cancer & Blood Center, LLC ( Site 1381)

    Athens, Georgia, 30607

  • St. Vincent Frontier Cancer Center-Research ( Site 1414)

    Billings, Montana, 59102

  • Providence Saint Joseph Medical Center, Disney Family Cancer ( Site 1392)

    Burbank, California, 91505

  • University of Chicago ( Site 1357)

    Chicago, Illinois, 60637

  • UC Health Memorial Hospital ( Site 1401)

    Colorado Springs, Colorado, 80909

  • Poudre Valley Health System ( Site 1402)

    Fort Collins, Colorado, 80528

  • St Joseph Heritage Healthcare-Oncology ( Site 1383)

    Fullerton, California, 92835

  • West Cancer Center - East Campus ( Site 1396)

    Germantown, Tennessee, 38138

  • CHI Health St. Francis ( Site 1406)

    Grand Island, Nebraska, 68803

  • Cancer & Hematology Centers of Western Michigan ( Site 1358)

    Grand Rapids, Michigan, 49503

  • Hattiesburg Clinic Hematology/Oncology ( Site 1418)

    Hattiesburg, Mississippi, 39401

  • Cancer Partners of Nebraska ( Site 1353)

    Lincoln, Nebraska, 68510

  • James Graham Brown Cancer Center ( Site 1393)

    Louisville, Kentucky, 40202

  • Vanderbilt University Medical Center ( Site 1362)

    Nashville, Tennessee, 37232

  • University Medical Center New Orleans ( Site 1365)

    New Orleans, Louisiana, 70112

  • Illinois Cancer Care, PC ( Site 1352)

    Peoria, Illinois, 61615

  • Allegheny Singer Research Institute ( Site 1364)

    Pittsburgh, Pennsylvania, 15212

  • Providence Portland Medical Center ( Site 1400)

    Portland, Oregon, 97213

  • Oregon Health & Science University ( Site 1411)

    Portland, Oregon, 97232

  • Blue Ridge Cancer Care ( Site 1374)

    Roanoke, Virginia, 24014

  • New England Cancer Specialists ( Site 1422)

    Scarborough, Maine, 04074

  • Washington University in St. Louis ( Site 1384)

    St Louis, Missouri, 63110

  • Baylor Scott & White Medical Center - Temple ( Site 1397)

    Temple, Texas, 76508

Other trials in United States

Turkey (Türkiye)11 sites

  • Baskent University Adana Training Hospital ( Site 1205)

    Adana, 01250

  • Hacettepe University Faculty of Medicine ( Site 1200)

    Ankara, 06230

  • Gazi Universitesi Tip Fakultesi ( Site 1215)

    Ankara, 06500

  • Trakya Universitesi Tip Fakultesi ( Site 1210)

    Edirne, 22030

  • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1202)

    Istanbul, 34098

  • Prof. Dr. Cemil Tascioglu Sehir Hastanesi ( Site 1216)

    Istanbul, 34384

  • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1214)

    Istanbul, 34722

  • Kartal Dr. Lutfi Kirdar Egitim ve Arast Hast ( Site 1211)

    Istanbul, 34890

  • Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi ( Site 1204)

    Izmir, 35040

  • Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1203)

    Konya, 42080

  • Inonu Universitesi Medical Fakultesi ( Site 1207)

    Malatya, Adana, 44280

Other trials in Turkey (Türkiye)

Japan10 sites

  • Chiba Cancer Center ( Site 0656)

    Chiba, 260-8717

  • National Hospital Organization Kyushu Cancer Center ( Site 0654)

    Fukuoka, 811-1395

  • National Cancer Center Hospital East ( Site 0650)

    Kashiwa, Chiba, 2778577

  • St. Marianna University School of Medicine Hospital ( Site 0657)

    Kawasaki, Kanagawa, 216-8511

  • Saitama Cancer Center ( Site 0653)

    Kitaadachi-gun, Saitama, 362-0806

  • National Hospital Organization Shikoku Cancer Center ( Site 0652)

    Matsuyama, Ehime, 791-0280

  • Aichi Cancer Center Hospital ( Site 0658)

    Nagoya, Aichi-ken, 464-8681

  • Shizuoka Cancer Center Hospital and Research Institute ( Site 0655)

    Sunto-gun, Shizuoka, 411-8777

  • National Cancer Center Hospital ( Site 0651)

    Tokyo, 104-0045

  • The Cancer Institute Hospital of JFCR ( Site 0659)

    Tokyo, 135-8550

Other trials in Japan

Russia9 sites

  • Arkhangelsk Clinical Oncological Dispensary ( Site 1113)

    Arkhangelsk, Arkhangelskaya oblast, 163045

  • MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 1129)

    Krasnogorsk, Moscow Oblast, 143442

  • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1121)

    Krasnoyarsk, Krasnoyarsk Krai, 660133

  • National Medical and Surgical Center n.a. N.I.Pirogov ( Site 1126)

    Moscow, Moscow, 105203

  • N.N. Blokhin NMRCO ( Site 1106)

    Moscow, Moscow, 115478

  • First Moscow State Medical University n.a. I.M.Sechenov ( Site 1127)

    Moscow, Moscow, 119991

  • MROI n.a. P.A. Herzen - branch of FSBI NMICR of MoH of Russia ( Site 1128)

    Moscow, Moscow, 125284

  • City Clinical Oncology Center ( Site 1114)

    Saint Petersburg, Sankt-Peterburg, 198255

  • GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1130)

    Ufa, Baskortostan, Respublika, 450054

Other trials in Russia

Belgium8 sites

  • OLV Ziekenhuis ( Site 0109)

    Aalst, Oost-Vlaanderen, 9300

  • Imelda vzw ( Site 0110)

    Bonheiden, Antwerpen, 2820

  • AZ Klina ( Site 0106)

    Brasschaat, Antwerpen, 2930

  • UCL Saint Luc ( Site 0100)

    Brussels, Bruxelles-Capitale, Region de, 1200

  • UZ Antwerpen ( Site 0108)

    Edegem, Antwerpen, 2650

  • UZ Gent ( Site 0101)

    Ghent, Oost-Vlaanderen, 9000

  • AZ Groeninge ( Site 0105)

    Kortrijk, West-Vlaanderen, 8500

  • UZ Gasthuisberg ( Site 0102)

    Leuven, Vlaams-Brabant, 3000

Other trials in Belgium

Ukraine8 sites

  • Medical center Medikal Plaza of Ecodnipro LLC ( Site 1317)

    Dnipro, Dnipropetrovsk Oblast, 49055

  • Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1319)

    Kapitanivka Village, Kyivska Oblast, 08111

  • Communal non profit enterprise Regional Clinical Oncology Center ( Site 1304)

    Kharkiv, Kharkiv Oblast, 61070

  • Medical Center Asklepion LLC ( Site 1309)

    Khodosovka, Kyivska Oblast, 08173

  • Medical Center Verum ( Site 1318)

    Kyiv, Kyivska Oblast, 03039

  • Shalimov s NI of Surgery and Transplantation ( Site 1321)

    Kyiv, Kyivska Oblast, 03126

  • Dobrobut Medical Center ( Site 1320)

    Kyiv, 03151

  • Medical center of the Limited Liability Company Yulis ( Site 1314)

    Zaporizhzhya, Zaporizhzhia Oblast, 69035

Other trials in Ukraine

Colombia7 sites

  • Administradora Country SA - Clinica del Country ( Site 0350)

    Bogotá, Bogota D.C., 110221

  • Instituto Nacional de Cancerologia E.S.E ( Site 0362)

    Bogotá, Bogota D.C., 110321

  • Fundacion Cardiovascular de Colombia ( Site 0360)

    Bucaramanga, Santander Department, 681002

  • Hemato Oncologos S.A. ( Site 0355)

    Cali, Valle del Cauca Department, 760042

  • Oncomedica S.A. ( Site 0352)

    Montería, Departamento de Córdoba, 230002

  • Oncologos del Occidente ( Site 0364)

    Pereira, Risaralda Department, 660001

  • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0353)

    Valledupar, Cesar Department, 200001

Other trials in Colombia

France7 sites

  • CHU Jean Minjoz ( Site 0450)

    Besançon, Doubs, 25000

  • Centre Leon Berard ( Site 0459)

    Lyon, Auvergne-Rhône-Alpes, 69008

  • CHU Saint Eloi ( Site 0467)

    Montpellier, Herault, 34295

  • Hopital Europeen Georges Pompidou ( Site 0452)

    Paris, 75015

  • CHU Bordeaux Haut-Leveque ( Site 0457)

    Pessac, Gironde, 33604

  • Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0455)

    Saint-Herblain, Brittany Region, 44805

  • C.H.U. de Strasbourg Hopital de Hautepierre ( Site 0464)

    Strasbourg, Bas-Rhin, 67098

Other trials in France

South Korea7 sites

  • Kyungpook National University Chilgok Hospital ( Site 0956)

    Daegu, Taegu-Kwangyokshi, 41404

  • Korea University Anam Hospital ( Site 0955)

    Seoul, 02841

  • Seoul National University Hospital ( Site 0950)

    Seoul, 03080

  • Severance Hospital Yonsei University Health System ( Site 0951)

    Seoul, 03722

  • Samsung Medical Center ( Site 0954)

    Seoul, 06351

  • The Catholic University of Korea St. Mary s Hospital ( Site 0953)

    Seoul, 06591

  • Asan Medical Center ( Site 0952)

    Songpagu, Seoul, 05505

Other trials in South Korea

Australia6 sites

  • Monash Health ( Site 0050)

    Clayton, Victoria, 3168

  • Peninsula Health Frankston Hospital ( Site 0056)

    Frankston, Victoria, 3199

  • Royal Brisbane and Women s Hospital ( Site 0054)

    Herston, Queensland, 4029

  • St George Hospital ( Site 0052)

    Kogarah, New South Wales, 2217

  • Liverpool Hospital ( Site 0055)

    Liverpool, New South Wales, 2170

  • Queen Elizabeth Hospital ( Site 0053)

    Woodville South, South Australia, 5011

Other trials in Australia

Canada6 sites

  • Dr. Everett Chalmers Regional Hospital ( Site 0204)

    Fredericton, New Brunswick, E3B 5N5

  • Hopital Cite de la Sante de Laval ( Site 0203)

    Laval, Quebec, H7M 3L9

  • Moncton Hospital - Horizon Health Network ( Site 0201)

    Moncton, New Brunswick, E1C 6Z8

  • McGill University Health Centre ( Site 0207)

    Montreal, Quebec, H4A 3J1

  • CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0202)

    Sherbrooke, Quebec, J1H 5N4

  • Princess Margaret Cancer Centre ( Site 0209)

    Toronto, Ontario, M5G 1X6

Other trials in Canada

Hungary6 sites

  • Orszagos Onkologiai Intezet ( Site 1431)

    Budapest, 1122

  • Debreceni Egyetem Klinikai Kozpont ( Site 1426)

    Debrecen, Hajdú-Bihar, 4032

  • Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 1432)

    Gyula, Bekes County, 5700

  • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce

    Miskolc, Borsod-Abauj Zemplen county, 3526

  • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1427)

    Szolnok, Jász-Nagykun-Szolnok, 5000

  • Zala Megyei Szent Rafael Korhaz ( Site 1429)

    Zalaegerszeg, Zala County, 8900

Other trials in Hungary

Spain5 sites

  • Hospital Vall D Hebron ( Site 1151)

    Barcelona, 08035

  • Hospital General Universitario de Elche ( Site 1155)

    Elche, Alicante, 03203

  • Hospital Universitario Gregorio Maranon ( Site 1152)

    Madrid, 28009

  • Hospital 12 de Octubre de Madrid ( Site 1150)

    Madrid, 28041

  • Hospital Universitario Central de Asturias ( Site 1153)

    Oviedo, Principality of Asturias, 33011

Other trials in Spain

Germany4 sites

  • Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0504)

    Berlin, 10117

  • St. Josef und St. Elisabeth Hospital gGmbH-Hematology, oncology and palliative medicine ( Site 0503)

    Bochum, North Rhine-Westphalia, 44791

  • Facharztzentrum Eppendorf ( Site 0501)

    Hamburg, 20249

  • Universitaetsklinikum Ulm ( Site 0500)

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Chile3 sites

  • Sociedad Oncovida S.A. ( Site 0250)

    Santiago, Region M. de Santiago, 7510032

  • Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0252)

    Santiago, Region M. de Santiago, 7620002

  • Centro Investigación del Cáncer James Lind ( Site 0251)

    Temuco, Araucania, 4780000

Other trials in Chile

Latvia3 sites

  • Daugavpils Regional Hospital ( Site 1502)

    Daugavpils, 5417

  • P. Stradina Clinical University Hospital ( Site 1500)

    Riga, LV-1002

  • Riga East Clinical University Hospital ( Site 1501)

    Riga, LV-1079

Other trials in Latvia

Lithuania3 sites

  • LSMUL Kauno Klinikos ( Site 1528)

    Kaunas, 50161

  • Nacionalinis Vezio Institutas ( Site 1527)

    Vilnius, 08406

  • Vilniaus Universiteto Ligonine Santaros Klinikos ( Site 1526)

    Vilnius, 08460

Other trials in Lithuania

South Africa3 sites

  • The Oncology Centre ( Site 0903)

    Durban, Limpopo, 4001

  • Cancercare Rondebosch Oncology ( Site 0904)

    Rondebosch, Western Cape, 7700

  • Sandton Oncology Medical Group PTY LTD ( Site 0900)

    Sandton, Gauteng, 2196

Other trials in South Africa

About this study

Official title: A Phase 3 Randomized, Open-label Study to Evaluate the Efficacy and Safety of Olaparib Alone or in Combination With Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Participants With Unresectable or Metastatic Colorectal Cancer Who Have Not Progressed Following First-line Induction (LYNK-003)

This is an efficacy and safety study of olaparib alone or in combination with bevacizumab being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. The primary hypotheses are: Olaparib + Bevacizumab is superior to a fluoropyrimidine + Bevacizumab with respect to progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR); Olaparib is superior to a fluoropyrimidine + Bevacizumab with respect to PFS using RECIST 1.1 as assessed by BICR. As of amendment 5 study enrollment is being discontinued and study participants randomized to one of the two experimental arms (olaparib plus bevacizumab or olaparib monotherapy) must discontinue study intervention. Participants who are still on study treatment will no longer have tumor response assessments by BICR.

Being tested
Olaparib, 5-FU, Bevacizumab, Capecitabine, Leucovorin/ levoleucovorin
Keywords
colorectal cancer, CRC, Olaparib, Bevacizumab, FOLFOX, 5-FU, fluorouracil, folinic acid, oxaliplatin, CAPOX, capecitabine
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • OlaparibDrug

    Also called LYNPARZA^TM

    300 mg BID, oral until progressive disease or end of study

  • 5-FUDrug

    Also called Fluorouracil, Adrucil, Efudex

    2400 mg/m^2 over 46 to 48 hours Q2W IV infusion until disease progression or end of study; bolus 5-FU (400mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion

  • BevacizumabDrug

    Also called MVASI^TM, Avastin

    5 mg/kg or 7.5 mg/kg Q2W or Q3W IV infusion until progressive disease or end of study

  • CapecitabineDrug

    Also called XELODA^®

    1000 mg/m^2 oral capsule BID for 14 days, then 7 days off, Q3W) until progressive disease or end of study

  • Leucovorin/ levoleucovorinDrug

    Also called Folinic Acid, Fusilev^®, Khapzory^TM

    400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) may be added to Bevacizumab + 5-FU per investigator's discretion Q2W IV infusion until progressive disease or end of study

Study groups in NCT04456699
Study groupRoleWhat they receive
Olaparib + bevacizumabExperimentalParticipants will receive olaparib (300 mg twice daily [BID] oral) + Bevacizumab (5 mg/kg intravenous [IV] once every 2 weeks [Q2W]) until progressive disease or end of study.
Receives: Drug: Olaparib; Drug: Bevacizumab
OlaparibExperimentalParticipants will receive olaparib (300 mg BID) oral, until progressive disease or end of study.
Receives: Drug: Olaparib
Bevacizumab + chemotherapyActive comparatorParticipants will receive investigator's choice of either bevacizumab (7.5 mg/kg IV once every three weeks (Q3W)) + capecitabine (1000 mg/m^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5-FU (400 mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.
Receives: Drug: 5-FU; Drug: Bevacizumab; Drug: Capecitabine; Drug: Leucovorin/ levoleucovorin

What is being measured

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

  1. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)

    PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS using RECIST 1.1 as assessed by BICR is presented.

    Measured: Up to approximately 30 months

Secondary outcomes (5)

  1. Overall Survival (OS)

    OS was defined as the time from randomization to death due to any cause. The OS is presented.

    Measured: Up to approximately 30 months

  2. Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

    ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

    Measured: Up to approximately 30 months

  3. Number of Participants With One or More Adverse Events (AE)

    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced at least one AE was reported for each arm.

    Measured: Up to approximately 30 months

  4. Number of Participants Discontinuing Study Intervention Due to an AE

    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study intervention due to an AE was reported for each arm.

    Measured: Up to approximately 30 months

  5. Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

    For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. DOR is defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis will be censored at the date of their last tumor assessment. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions is also considered PD. DOR assessments will be based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experience a confirmed CR or PR will be presented.

    Measured: Up to approximately 30 months

Timeline

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

  1. First posted2 Jul 2020
  2. Study start19 Aug 2020
  3. Primary completion27 Mar 2023
  4. Study completion6 Nov 2023

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
335 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04456699
Sponsor's protocol ID
7339-003
Other IDs
MK-7339-003, LYNK-003, jRCT2031200146, 2019-000698-22, 2019
Status last verified
Oct 2024
First submitted
1 Jul 2020
Last updated
29 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Takashima A, Garcia-Alfonso P, Manneh R, Besen AA, Hong YS, Cuyle PJ, Yanez P, Burge M, Yoshino T, Kim TW, Cui K, Li C, Jain R, Adelberg D, Taieb J. Olaparib with or without bevacizumab versus bevacizumab plus a fluoropyrimidine as maintenance therapy in advanced colorectal cancer: The randomized phase 3 LYNK-003 study. Eur J Cancer. 2024 Jul;205:114036. doi: 10.1016/j.ejca.2024.114036. Epub 2024 Mar 21.

    PubMed 38749110

  • Kim TW, Taieb J, Gurary EB, Lerman N, Cui K, Yoshino T. Olaparib with or without bevacizumab or bevacizumab and 5-fluorouracil in advanced colorectal cancer: Phase III LYNK-003. Future Oncol. 2021 Dec;17(36):5013-5022. doi: 10.2217/fon-2021-0899. Epub 2021 Nov 15.

    PubMed 34779646

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Olaparib, 5-FU and Bevacizumab in people with Metastatic Colorectal Cancer, run by Merck Sharp & Dohme LLC at 129 sites in 18 countries.

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 10 inclusion and 23 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 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 129 sites in United States, Turkey (Türkiye), Japan, Russia, Belgium and 13 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) (time frame: Up to approximately 30 months). 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 NCT04456699, which also lists 2 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 29 Oct 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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