Clinical trial NCT03742895: Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)
Official title: A Phase 2 Study of Olaparib Monotherapy in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Solid Neoplasms
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2018-11-15
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of olaparib (MK-7339) monotherapy in participants with multiple types of advanced cancer (unresectable and/or metastatic) that: 1) have progressed or been intolerant to standard of care therapy; and 2) are positive for homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).


Eligibility criteria: Inclusion Criteria:

* For all participants:
* Has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the local site Investigator/radiology and confirmed by BICR.
* Is able to provide a newly obtained core or excisional biopsy of a tumor lesion or either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or slides.
* Has a life expectancy of at least 3 months.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 7 days of treatment initiation.
* Male participants must agree to use contraception during the treatment period and for at least 95 days (3 months and 5 days) after the last dose of study treatment and refrain from donating sperm during this period.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

  1. Is not a woman of childbearing potential (WOCBP).
  2. Is a WOCBP and using a contraceptive method that is highly effective with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days after the last dose of study intervention, AND agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. Abstains from breastfeeding during the study intervention period and for at least 30 days after the last dose of study intervention.
* Has adequate organ function.
* For participants who have non-breast or -ovarian cancers that are breast cancer susceptibility gene 1/2 (BRCA1/2) mutated (BRCAm), or who have cancers that are BRCA1/2 non-mutated and homologous recombination repair nonmutated:
* Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except ovarian cancer whose tumor has a germline or somatic BRCA mutation and breast cancer whose tumor has a germline 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 at least 1 of the genes involved in HRR or centrally-confirmed HRD.
* For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor, have no evidence of disease progression during the platinum chemotherapy or ≤4 weeks of completing the platinum-containing regimen.
* For participants who have somatic BRCAm breast cancer:
* Has histologically- or cytologically-confirmed breast cancer with evidence of metastatic disease.
* Has a known or suspected deleterious mutation in breast cancer susceptibility gene (BRCA) 1 or BRCA2 and does not harbor a germline BRCA1 or BRCA2 mutation - testing can be done centrally or locally. Blood and tissue samples must be provided by all participants.
* Has received treatment with an anthracycline unless contraindicated and a taxane in either the neoadjuvant/adjuvant or metastatic setting.
* Participants with estrogen and/or progesterone receptor-positive disease must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.

Exclusion Criteria:

* Has a known additional malignancy that is progressing or has required active treatment in the last 5 years. Note: 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 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. Note: Participants with previously treated brain metastases may participate if radiologically stable, clinically stable, and without requirement for steroid treatment for at least 14 days prior to the first dose of study treatment.
* 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 infection (i.e., Hepatitis B or C).
* Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
* Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (poly\[ADP ribose\]) polymerization (PARP) inhibitor.
* Has a known hypersensitivity to the components or excipients in olaparib.
* 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. Packed red blood cells and platelet transfusions are acceptable if not performed within 28 days of the first dose of study treatment.
* Has received any anti-neoplastic systemic chemotherapy or biological therapy, targeted therapy, or an anticancer hormonal therapy within 3 weeks prior to the first dose of study intervention.
* Has a primary cancer of unknown origin.
* Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 53 months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to 53 months
measure: Overall Survival (OS)
timeFrame: Up to 53 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 53 months
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 53 months
measure: Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE)
timeFrame: Up to 52 months
measure: Objective Response Rate (ORR) in Participants with HRRm or HRD Positive Cancer
timeFrame: Up to 53 months
measure: Time to Earliest Progression by Cancer Antigen-125 (CA-125)
timeFrame: Up to 53 months
measure: Prostate-specific Antigen (PSA) Response Rate in Participants with Prostate Cancer
timeFrame: Up to 53 months
measure: Progression-Free Survival After Next-Line Treatment in Participants with sBRCAm Breast Cancer
timeFrame: Up to 53 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center - North Campus ( Site 0011)
state: Arizona
city: Fullerton
country: United States
facility: St Joseph Heritage Healthcare-Oncology ( Site 0056)
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center ( Site 0002)
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0007)
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional Veterans Affairs Medical Center ( Site 0092)
state: Colorado
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University ( Site 0025)
state: Georgia
city: Augusta
country: United States
facility: Augusta University ( Site 0028)
state: Georgia
city: Lexington
country: United States
facility: Markey Cancer Center ( Site 0018)
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland ( Site 0050)
state: Maryland
city: Baltimore
country: United States
facility: Weinberg Cancer Institute at Franklin Square ( Site 0054)
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts ( Site 0017)
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System ( Site 0060)
state: Michigan
city: Lincoln
country: United States
facility: Cancer Partners of Nebraska ( Site 0051)
state: Nebraska
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0116)
state: New Jersey
city: Harrison
country: United States
facility: Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 0126)
state: New York
city: New York
country: United States
facility: VA New York Harbor Healthcare System Manhattan ( Site 0094)
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0057)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center ( Site 0026)
state: New York
city: Tulsa
country: United States
facility: Southwestern Regional Medical Center, Inc. ( Site 0079)
state: Oklahoma
city: Philadelphia
country: United States
facility: Eastern Regional Medical Center, Inc. ( Site 0077)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Hematology Oncology-Sioux Falls SD ( Site 0012)
state: South Dakota
city: Saint George
country: United States
facility: Intermountain Healthcare ( Site 0043)
state: Utah
city: Seattle
country: United States
facility: Virginia Mason Medical Center ( Site 0052)
state: Washington
city: Seattle
country: United States
facility: Veterans Affairs Puget Sound Health Care System [Seattle, WA] ( Site 0093)
state: Washington
city: Berazategui
country: Argentina
facility: Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 2703)
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires ( Site 2704)
state: Caba
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas ( Site 2700)
city: Buenos Aires
country: Argentina
facility: Hospital Aleman ( Site 2702)
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre ( Site 2200)
state: New South Wales
city: Port Macquarie
country: Australia
facility: MNCCI Port Macquarie Base Hospital ( Site 2201)
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd ( Site 2202)
state: Western Australia
city: Toronto
country: Canada
facility: Sunnybrook Research Institute ( Site 0210)
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0203)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0209)
state: Quebec
city: Quebec
country: Canada
facility: Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
city: Medellin
country: Colombia
facility: Fundacion Centro de Investigacion Clinica CIC ( Site 2812)
state: Antioquia
city: Medellin
country: Colombia
facility: Rodrigo Botero SAS ( Site 2801)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Biomelab S A S ( Site 2800)
state: Atlantico
city: Valledupar
country: Colombia
facility: Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2808)
state: Cesar
city: Monteria
country: Colombia
facility: Oncomedica S.A. ( Site 2806)
state: Cordoba
city: Bogota
country: Colombia
facility: Administradora Country SA - Clinica del Country ( Site 2802)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2807)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Instituto Nacional de Cancerologia E.S.E ( Site 2809)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: C. Medico Imbanaco Cali S.A. ( Site 2810)
state: Valle Del Cauca
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 0402)
state: Hovedstaden
city: Herlev
country: Denmark
facility: Herlev og Gentofte Hospital. ( Site 0401)
state: Hovedstaden
city: Odense
country: Denmark
facility: Odense Universitetshospital ( Site 0400)
state: Syddanmark
city: Poitiers
country: France
facility: CHU Poitiers ( Site 0612)
state: Ain
city: Nice
country: France
facility: Centre Antoine Lacassagne ( Site 0610)
state: Alpes-Maritimes
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe ( Site 0613)
state: Alsace
city: Dijon
country: France
facility: Centre Georges Francois Leclerc ( Site 0608)
state: Bourgogne
city: Bordeaux
country: France
facility: Institut Bergonie ( Site 0603)
state: Gironde
city: Villejuif
country: France
facility: Institut Gustave Roussy ( Site 0601)
state: Val-de-Marne
city: Guatemala
country: Guatemala
facility: Centro Regional de Sub Especialidades Medicas SA ( Site 3003)
state: Quetzaltenango
city: Guatemala
country: Guatemala
facility: Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 3004)
city: Guatemala
country: Guatemala
facility: Integra Cancer Institute ( Site 3006)
city: Guatemala
country: Guatemala
facility: Grupo Angeles SA ( Site 3001)
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital ( Site 1654)
state: Carlow
city: Cork
country: Ireland
facility: Bon Secours Hospital ( Site 1656)
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital ( Site 1653)
city: Dublin
country: Ireland
facility: Tallaght University Hospital ( Site 1652)
city: Beer-Sheva
country: Israel
facility: Soroka Medical Center ( Site 0800)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology Division ( Site 0801)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 0802)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 0803)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0804)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Pascale ( Site 0700)
state: Campania
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas Research Hospital ( Site 0703)
state: Lombardia
city: Siena
country: Italy
facility: Policlinico Le Scotte di Siena ( Site 0704)
state: Toscana
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital ( Site 2602)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 2600)
state: Chiba
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital ( Site 2603)
state: Kyoto
city: Suita
country: Japan
facility: Osaka University Hospital ( Site 2604)
state: Osaka
city: Tokyo
country: Japan
facility: National Cancer Center Hospital ( Site 2601)
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR ( Site 2605)
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 2402)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 2401)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 2400)
city: Guadalajara
country: Mexico
facility: Actualidad Basada en la Investigacion del Cancer ( Site 2903)
state: Jalisco
city: Monterrey
country: Mexico
facility: Unidad Biomedica Avanzada Monterrey S. A. ( Site 2902)
state: Nuevo Leon
city: Santiago De Quetaro
country: Mexico
facility: Cuidados Oncologicos ( Site 2908)
state: Queretaro
city: Madero
country: Mexico
facility: Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 2901)
state: Tamaulipas
city: Chihuahua
country: Mexico
facility: Centro Estatal de Cancerologia de Chihuahua ( Site 2907)
city: Mexico City
country: Mexico
facility: CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 2900)
city: Mexico
country: Mexico
facility: CENEIT Oncologicos ( Site 2904)
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization S.C. ( Site 2905)
city: Trujillo
country: Peru
facility: Hospital de Alta Complejidad de La Libertad Virgen de La Puerta ( Site 3102)
state: La Libertad
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas ( Site 3106)
state: Muni Metro De Lima
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen ( Site 3107)
city: Lima
country: Peru
facility: Clinica Internacional Sede San Borja ( Site 3100)
city: Lima
country: Peru
facility: Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 3101)
city: Lima
country: Peru
facility: Oncosalud-Clinical Research ( Site 3108)
city: Lima
country: Peru
facility: Hospital Central de la Fuerza Aerea del Peru ( Site 3104)
city: Lima
country: Peru
facility: Hospital Militar Central Coronel Luis Arias Schereiber ( Site 3105)
city: Lima
country: Peru
facility: Hospital Arzobispo Loayza ( Site 3103)
city: Oradea
country: Romania
facility: S.C. Pelican Impex S.R.L Spitalul Clinic Pelican Oradea ( Site 1102)
state: Bihor
city: Cluj Napoca
country: Romania
facility: Medisprof ( Site 1107)
state: Cluj
city: Comuna Floresti
country: Romania
facility: SC Radiotherapy Center Cluj SRL ( Site 1105)
state: Cluj
city: Craiova
country: Romania
facility: S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1103)
state: Dolj
city: Brasov
country: Romania
facility: Spitalul PDR Medlife ( Site 1106)
city: Bucuresti
country: Romania
facility: S.C.Focus Lab Plus S.R.L ( Site 1101)
city: Bucuresti
country: Romania
facility: S.C.Gral Medical S.R.L ( Site 1104)
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Clinical Oncological Dispensary ( Site 1204)
state: Arkhangel Skaya Oblast
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1212)
state: Chelyabinskaya Oblast
city: Krasnogorsk
country: Russian Federation
facility: MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 1216)
state: Moskovskaya Oblast
city: Moscow
country: Russian Federation
facility: N.N. Blokhin NMRCO ( Site 1201)
state: Moskva
city: Moscow
country: Russian Federation
facility: MSROI named after P.A. Hertsen branch of FSBI NMRC Radiology ( Site 1213)
state: Moskva
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Oncology dispensary ( Site 1202)
state: Ryazanskaya Oblast
city: Samara
country: Russian Federation
facility: SBHI Samara Regional Clinical Oncology Dispensary ( Site 1211)
state: Samarskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1208)
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: Clinical Hospital Saint Luka ( Site 1205)
state: Sankt-Peterburg
city: St.Petersburg
country: Russian Federation
facility: SBHI Leningrad Regional Clinical Hospital ( Site 1206)
state: Sankt-Peterburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Tatarstan MoH named after professor M.Z. Sigal ( Site 120
state: Tatarstan, Respublika
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid ( Site 1352)
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron ( Site 1350)
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich ( Site 1400)
state: Aargau
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve HUG. ( Site 1406)
state: Geneve
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale di Bellinzona e Valli ( Site 1407)
state: Ticino
city: Konya
country: Turkey
facility: Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1507)
state: Adana
city: Adana
country: Turkey
facility: Baskent University Adana Training Hospital ( Site 1508)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tıp Fakultesi ( Site 1503)
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi ( Site 1504)
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi ( Site 1500)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1505)
city: Istanbul
country: Turkey
facility: Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1506)
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi ( Site 1502)
city: Oxford
country: United Kingdom
facility: Churchill Hospital ( Site 1606)
state: Worcestershire
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust ( Site 1601)
city: Newcastle Upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Care ( Site 1602)
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital ( Site 1607)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: