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Active (not recruiting) Phase 2 NCT04123366

Study of Olaparib (MK-7339) in Combination With Pembrolizumab (MK-3475) in the Treatment of Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer (MK-7339-007/KEYLYNK-007)

Phase 2 – studying effectiveness and dosage
Conditions: Solid Tumors

Sponsor: Merck Sharp & Dohme LLC

trial.available_in: БГ
Overview
The purpose of this study is to assess the efficacy and safety of treatment with olaparib (MK-7339) in combination with pembrolizumab (MK-3475) in adults with previously treated, advanced (metastatic and/or unresectable) Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-positive solid tumors.
Who can participate
Inclusion Criteria: * Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline or somatic BRCA mutation) that is not eligible for curative treatment and for which standard of care therapy has failed. Participants must have progressed on or be intolerant to standard of care therapies that are known to provide clinical benefit. There is no limit on the number of prior treatment regimens. * Has either centrally-confirmed known or suspected deleterious mutations in ≥1 of the specified 15 genes involved in HRR or centrally-confirmed HRD based on the Lynparza HRR-HRD assay. * Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology and confirmed in real time by blinded independent central review (BICR). BICR must confirm the presence of radiologically measurable disease per RECIST 1.1 for the participant to be eligible for the study. * Has a life expectancy of ≥3 months. * Must have had CR or PR while on the last treatment with prior cisplatin or carboplatin, or if received only oxaliplatin had CR, PR, or stable disease (SD) while on the last treatment with prior oxaliplatin (either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor. Participant must also not have been refractory to prior platinum-containing therapy. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of study treatment initiation. * Male participants must agree to use contraception during the treatment period and for ≥90 days (3 months) after the last dose of olaparib and refrain from donating sperm during this period. * Female participants must not be pregnant or breastfeeding, and ≥1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP who agrees to use contraception during the treatment period and for ≥120 days (3 months) after the last dose of pembrolizumab and 180 days (6 months) after the last dose of olaparib, has a highly sensitive pregnancy test within 24 hours for urine or within 72 hours for serum before the first dose of study intervention, and abstains from breastfeeding during the study intervention period and for at least 120 days after the last dose of the study intervention. * Has adequate organ function Exclusion Criteria: * Has a known additional malignancy that is progressing or has required active treatment in the last 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded. * Has a history of non-infectious pneumonitis/interstitial lung disease that required treatment with steroids or currently has pneumonitis/interstitial lung disease. * Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML. * Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has an active infection requiring systemic therapy. * Has active tuberculosis (Bacillus tuberculosis \[TB\]). * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing \>10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. * Has an active autoimmune disease that has required systemic treatment in the past 2 years. * Has received colony-stimulating factors (e.g. granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\] or recombinant erythropoietin) within 28 days prior to the first dose of study treatment. * Has a known history of human immunodeficiency virus (HIV) infection. * Has known active hepatitis B or hepatitis C. * Is unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption). * Has received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-programmed death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX 40 \[Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)\], CD137 \[tumor necrosis factor receptor superfamily member 9 (TNFRSF9)\]). * Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (poly\[ADP ribose\]) polymerization (PARP) inhibitor. * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to administration of study treatment. * Must have recovered from all adverse events (AEs) due to previous therapies, excluding alopecia, to ≤Grade 1 or Baseline. * Has a known hypersensitivity to the study treatments and/or any of their excipients. * Is currently receiving either strong inhibitors of cytochrome P450 (CYP)3A4 (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate inhibitors of CYP3A4 (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks. * Is currently receiving either strong inducers of CYP3A4 (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate inducers of CYP3A4 (e.g. bosentan, efavirenz, modafinil) that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents. * Has received previous allogenic bone-marrow transplant or double umbilical cord transplantation (dUCBT). * Has received a whole blood transfusion in the last 120 days prior to entry to the study. * Has received prior radiotherapy within 2 weeks of start of study treatment. * Is currently enrolled in and receiving study therapy, was enrolled in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks (28 days) of the first dose of study treatment. * The presence of uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fredericia \[QTcF\] prolongation \>500 msec, electrolyte disturbances), or participant has congenital long QT syndrome. * Has either had major surgery within 2 weeks of starting study treatment or has not recovered from any effects of any major surgery. * Has received a live vaccine within 30 days prior to the first dose of study treatment. * Has had an allogenic tissue/solid tumor organ transplant.
Interventions
Olaparib
DRUG
Pembrolizumab
BIOLOGICAL
Locations 135
Argentina (5)
Centro Medico Dra De Salvo ( Site 2702)
Buenos Aires
CEMIC ( Site 2701)
Buenos Aires
Fundacion CIDEA ( Site 2704)
Ciudad de Buenos Aires , Buenos Aires F.D.
Hospital Britanico de Buenos Aires ( Site 2705)
Ciudad de Buenos Aires , Buenos Aires F.D.
Centro Oncologico Riojano Integral ( Site 2703)
La Rioja
Australia (4)
Blacktown Hospital ( Site 2202)
Blacktown , New South Wales
Monash Medical Centre ( Site 2205)
Clayton , Victoria
Linear Clinical Research Ltd ( Site 2206)
Nedlands , Western Australia
Tasman Oncology Research Pty Ltd ( Site 2203)
Southport , Queensland
Canada (3)
Moncton Hospital - Horizon Health Network ( Site 0206)
Moncton , New Brunswick
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0201)
Montreal , Quebec
BC Cancer-Vancouver Center ( Site 0203)
Vancouver , British Columbia
Colombia (5)
Clinica de la Costa S.A.S. ( Site 2900)
Barranquilla , Atlántico
Hemato Oncologos S.A. ( Site 2910)
Cali , Valle del Cauca Department
Fundacion Valle del Lili ( Site 2909)
Cali , Valle del Cauca Department
Fundación Colombiana de Cancerología Clínica Vida ( Site 2902)
Medellín , Antioquia
Fundacion Cardiovascular de Colombia ( Site 2907)
Piedecuesta , Santander Department
France (5)
CHU Jean Minjoz ( Site 0606)
Besançon , Doubs
CHD Vendee ( Site 0604)
La Roche-sur-Yon , Vendee
Institut du Cancer de Montpellier ( Site 0610)
Montpellier , Herault
Centre Henri Becquerel ( Site 0607)
Rouen , Seine-Maritime
Institut Gustave Roussy ( Site 0602)
Villejuif , Val-de-Marne
Germany (3)
Charite-Universitaetsmedizin Berlin-Campus Benjamin Franklin ( Site 0902)
Berlin
Universitaetsklinik Koeln ( Site 0903)
Cologne , North Rhine-Westphalia
Universitaetsklinik der Ludwig-Maximilians-Universitaet Muenchen ( Site 0906)
Munich , Bavaria
Guatemala (5)
Oncologika S.A. ( Site 3003)
Guatemala City
Grupo Angeles SA ( Site 3004)
Guatemala City
Sanatorio Nuestra Senora del Pilar ( Site 3006)
Guatemala City
Medi-K Cayala ( Site 3005)
Guatemala City
Centro Medico Integral De Cancerología (CEMIC) ( Site 3002)
Quetzaltenango
Israel (6)
Rambam Health Care Campus-Oncology Division ( Site 0801)
Haifa
Hadassah Ein Kerem Medical Center ( Site 0802)
Jerusalem
Meir Medical Center ( Site 0804)
Kfar Saba
Rabin Medical Center ( Site 0806)
Petah Tikva
Chaim Sheba Medical Center ( Site 0800)
Ramat Gan
Sourasky Medical Center ( Site 0805)
Tel Aviv
Italy (4)
ASST Grande Ospedale Metropolitano Niguarda ( Site 0700)
Milan
Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0703)
Modena , Emilia-Romagna
Istituto Nazionale Tumori Fondazione Pascale ( Site 0705)
Naples
Azienda Ospedaliera Universitaria Senese ( Site 0704)
Siena
Japan (7)
Kyushu University Hospital ( Site 2506)
Fukuoka
National Cancer Center Hospital East ( Site 2500)
Kashiwa , Chiba
Aichi Cancer Center Hospital ( Site 2504)
Nagoya , Aichi-ken
Okayama University Hospital ( Site 2505)
Okayama
Hokkaido University Hospital ( Site 2502)
Sapporo , Hokkaido
National Cancer Center Hospital ( Site 2501)
Tokyo
Japanese Foundation for Cancer Research ( Site 2503)
Tokyo
Latvia (4)
Daugavpils Regional Hospital ( Site 2104)
Daugavpils
Liepaja Regional Hospital ( Site 2101)
Liepāja
Riga East Clinical University Hospital ( Site 2103)
Riga
P. Stradina Clinical University Hospital ( Site 2102)
Riga
Mexico (7)
Preparaciones Oncologicas ( Site 3102)
León , Guanajuato
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 3101)
Madero , Tamaulipas
CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 3103)
Mexico City
Unidad Biomedica Avanzada Monterrey S. A. ( Site 3108)
Monterrey , Nuevo León
Clinica Integral Internacional de Oncologia S. de R.L. de C.V. ( Site 3107)
Puebla City
Hospital H+ Queretaro ( Site 3104)
Querétaro City , Querétaro
Centro Medico Zambrano Hellion ( Site 3105)
San Pedro Garza García , Nuevo León
Peru (8)
Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 3206)
Arequipa , Ariqipa
Hospital Nacional Daniel Alcides Carrion ( Site 3207)
Bellavista , Qallaw
Hospital Nacional Adolfo Guevara Velasco ( Site 3205)
Cuzco , Qusqu
Oncosalud ( Site 3200)
Lima
Instituto Nacional de Enfermedades Neoplasicas ( Site 3201)
Lima
Hospital Nacional Arzobispo Loayza ( Site 3208)
Lima
Clinica San Gabriel ( Site 3202)
Lima
Hospital Nacional Cayetano Heredia ( Site 3203)
Lima
Poland (2)
Uniwersyteckie Centrum Kliniczne ( Site 1809)
Gdansk , Pomeranian Voivodeship
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
Warsaw , Masovian Voivodeship
Puerto Rico (4)
Hematology and Oncology Institute ( Site 0504)
Manati
Ad-Vance Medical Research LLC ( Site 0505)
Ponce
Pan American Center for Oncology Trials LLC ( Site 0501)
Rio Piedras
FDI Clinical Research ( Site 0500)
San Juan
Romania (5)
Spitalul Judetean de Urgenta Alba Iulia ( Site 1107)
Alba Iulia , Alba
Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1101)
Cluj-Napoca , Cluj
Medisprof ( Site 1102)
Cluj-Napoca , Cluj
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1103)
Craiova , Dolj
Policlinica Oncomed SRL ( Site 1104)
Timișoara , Timiș County
South Africa (6)
Universitas Annex National Hospital ( Site 1902)
Bloemfontein , Free State
The Oncology Centre ( Site 1904)
Durban , KwaZulu-Natal
Wits Clinical Research ( Site 1906)
Parktown-Johannesburg , Gauteng
Mary Potter Oncology Centre, Little Company of Mary Hospital ( Site 1900)
Pretoria , Gauteng
Cancercare Rondebosch Oncology ( Site 1901)
Rondebosch , Western Cape
Vaal Triangle Oncology Centre ( Site 1905)
Vereeniging , Gauteng
South Korea (4)
Seoul National University Bundang Hospital ( Site 2403)
Seongnam-si , Kyonggi-do
Seoul National University Hospital ( Site 2402)
Seoul
Severance Hospital Yonsei University Health System ( Site 2400)
Seoul
Samsung Medical Center ( Site 2401)
Seoul
Spain (3)
Hospital Clinic i Provincial ( Site 1302)
Barcelona
Hospital General Universitario Gregorio Maranon ( Site 1300)
Madrid
Hospital Quiron de Madrid ( Site 1301)
Pozuelo de Alarcón , Madrid
Sweden (3)
Skanes Universitetssjukhus Lund. ( Site 2001)
Lund , Skåne County
Karolinska Universitetssjukhuset Solna ( Site 2000)
Solna , Stockholm County
Akademiska Sjukhuset ( Site 2002)
Uppsala , Uppsala County
Turkey (11)
Baskent University Adana Training Hospital ( Site 1509)
Adana
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1502)
Ankara
Gazi Universitesi Tip Fakultesi ( Site 1507)
Ankara
Ankara Sehir Hastanesi ( Site 1508)
Ankara
Akdeniz Universitesi Tıp Fakultesi ( Site 1503)
Antalya
Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1500)
Edirne
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1504)
Istanbul
Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi ( Site 1505)
Istanbul
Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi ( Site 1501)
Izmir
Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1510)
Konya
Inonu Universitesi Medical Fakultesi ( Site 1506)
Malatya
Ukraine (10)
Cherkasy Regional Oncology Dispensary ( Site 1702)
Cherkasy , Cherkasy Oblast
Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council ( Site 1700)
Dnipro , Dnipropetrovsk Oblast
Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Department for daily treated patient (
Ivano-Frankivsk , Ivano-Frankivsk Oblast
Communal non profit enterprise Regional Clinical Oncology Center ( Site 1704)
Kharkiv , Kharkivs’ka Oblast’
Khmelnitskiy Regional Onkology Dispensary ( Site 1705)
Khmelnitskiy , Khmelnytskyi Oblast
Kirovograd Regional oncology Dispensary ( Site 1716)
Kropyvnytsky , Kirovohrad Oblast
Medical Centre Consilium Medical ( Site 1712)
Kyiv , Kyivska Oblast
Podillya Regional Center of Oncology ( Site 1708)
Vinnytsia , Vinnytsia Oblast
Medical center of the Limited Liability Company Yulis ( Site 1714)
Zaporizhzhia , Zaporizhzhia Oblast
Zhytomyr Regional Oncology Center ( Site 1710)
Zhytomyr , Zhytomyr Oblast
United States (21)
Winship Cancer Institute of Emory University ( Site 0057)
Atlanta , Georgia
The Kirklin Clinic ( Site 0086)
Birmingham , Alabama
University Hospitals Cleveland Medical Center ( Site 0016)
Cleveland , Ohio
Parkland Health & Hospital System ( Site 0091)
Dallas , Texas
University of Texas, Southwestern Medical Center ( Site 0004)
Dallas , Texas
Inova Schar Cancer Institute ( Site 0008)
Fairfax , Virginia
University of Florida ( Site 0078)
Gainesville , Florida
Northeast Georgia Medical Center ( Site 0026)
Gainesville , Georgia
Banner MD Anderson Cancer Center ( Site 0049)
Gilbert , Arizona
Banner MD Anderson Cancer Center ( Site 0092)
Greeley , Colorado
University of Texas-MD Anderson Cancer Center ( Site 0087)
Houston , Texas
Norton Cancer Institute - St. Matthews ( Site 0024)
Louisville , Kentucky
Northwest Georgia Oncology Centers PC ( Site 0047)
Marietta , Georgia
The University of Oklahoma Health Sciences Center ( Site 0050)
Oklahoma City , Oklahoma
New York Cancer and Blood Specialists-Research Department ( Site 0080)
Port Jefferson Station , New York
UC Davis Comprehensive Cancer Center ( Site 0039)
Sacramento , California
San Francisco Oncology Associates ( Site 0085)
San Francisco , California
University of California San Francisco ( Site 0015)
San Francisco , California
Atlantic Health System ( Site 0046)
Summit , New Jersey
Northwest Medical Specialties, PLLC ( Site 0007)
Tacoma , Washington
Utah Cancer Specialists ( Site 0038)
West Valley City , Utah
Technical details
Status
Active (not recruiting)
Phase
Phase 2
Study type
INTERVENTIONAL
Sex
Male and female
Minimum age
18 Years
Healthy volunteers
No
Start date
18.11.2019
Completion date
29.06.2026
Registry ID
NCT04123366
Source
clinicaltrials.gov
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