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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03742895




Registration number
NCT03742895
Ethics application status
Date submitted
14/11/2018
Date registered
15/11/2018
Date last updated
8/08/2019

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
MK-7339-002
Secondary ID [2] 0 0
7339-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Olaparib

Experimental: Olaparib - Participants with HRRm or HRD-positive advanced cancer will receive oral olaparib, 300 mg twice daily (BID).


Treatment: Drugs: Olaparib
Olaparib 300 mg administered BID as two, 150 mg oral tablets.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) - ORR is defined as the percentage of participants who achieve a confirmed complete response ([CR]; disappearance of all target lesions) or partial response ([PR]: =30% decrease in the sum of diameters of target lesions) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). For participants with prostate cancer, ORR will be based on Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 as assessed by BICR.
Timepoint [1] 0 0
Up to 53 months
Secondary outcome [1] 0 0
Duration of Response (DOR) - DOR is defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death due to any cause, whichever occurs first. DOR will be assessed by BICR according to either RECIST 1.1 or PCWG-modified RECIST 1.1 for participants with prostate cancer.
Timepoint [1] 0 0
Up to 53 months
Secondary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the time from the date of the first dose to the date of death due to any cause.
Timepoint [2] 0 0
Up to 53 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS) - PFS is defined as the time from the date of the first dose to either: 1) the first documented disease progression as assessed either by BICR according to RECIST 1.1 or PCWG-modified RECIST 1.1 for participants with prostate cancer; or 2) death due to any cause, whichever occurs first.
Timepoint [3] 0 0
Up to 53 months
Secondary outcome [4] 0 0
Number of Participants Experiencing an Adverse Event (AE) - An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing an AE will be assessed.
Timepoint [4] 0 0
Up to 53 months
Secondary outcome [5] 0 0
Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE) - The number of participants discontinuing study treatment due to an AE will be assessed.
Timepoint [5] 0 0
Up to 52 months
Secondary outcome [6] 0 0
Time to Earliest Progression by Cancer Antigen-125 (CA-125) - For participants with BRCA1/2 non-mutated ovarian cancer only, the time to earliest progression by CA-125 will be assessed. Progression by CA-125 is defined as an increase in CA-125 level =2x upper limit normal (ULN) on 2 occasions, 1 week apart. For participants with elevated CA-125 (=ULN) at baseline, progression by CA-125 is defined as an increase in CA-125 level =2x the nadir value on 2 occasions, 1 week apart.
Timepoint [6] 0 0
Up to 53 months

Eligibility
Key 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 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.

- 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 3 days of treatment initiation.

- Male participants must agree to use contraception during the treatment period and for
at least 90 days (3 months) after the last dose of study treatment and refrain from
donating sperm during this period.

- Female participants must not be pregnant or breastfeeding. Additionally, female
participants must either not be a woman of childbearing potential (WOCBP) or, if a
WOCBP, agree to use contraception during the treatment period and for at least 30 days
(1 month) after the last dose of study treatment.

- Has adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SydneyWA
Recruitment hospital [1] 0 0
MNCCI Port Macquarie Base Hospital ( Site 2201) - Port Macquarie
Recruitment hospital [2] 0 0
Kinghorn Cancer Centre ( Site 2200) - Darlinghurst
Recruitment hospital [3] 0 0
Linear Clinical Research Ltd ( Site 2202) - Nedlands
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Georgia
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United States of America
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Kentucky
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Maryland
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Massachusetts
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Michigan
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Nebraska
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New York
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United States of America
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Oklahoma
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Pennsylvania
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South Dakota
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United States of America
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Utah
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United States of America
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Washington
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Argentina
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Buenos Aires
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Argentina
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Ciudad Autonoma de Buenos Aires
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Canada
State/province [16] 0 0
Quebec
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Colombia
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Antioquia
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Colombia
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Barranquilla
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Colombia
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Bogota
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Colombia
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Cali
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Colombia
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Monteria
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Denmark
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Copenhagen
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Denmark
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Herlev
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Denmark
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Odense
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France
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Bordeaux
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France
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Dijon
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France
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Nice
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France
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Poitiers
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France
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Strasbourg
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France
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Villejuif
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Guatemala
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Guatemala
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Guatemala
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Quetzaltenango
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Ireland
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Cork
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Ireland
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Dublin
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Napoli
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Italy
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Rozzano
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Italy
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Siena
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Japan
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Aichi
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Japan
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Chiba
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Osaka
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Kyoto
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Tokyo
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seoul
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Mexico
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Jalisco
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Mexico
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Nuevo Leon
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Tamaulipas
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Chihuahua
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Mexico
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Mexico City
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Oaxaca
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Mexico
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Santiago De Quetaro
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Peru
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La Libertad
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Peru
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Lima
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Romania
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Cluj
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Romania
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Dolj
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Romania
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Brasov
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Romania
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Bucuresti
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Russian Federation
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Arkhangelsk
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Russian Federation
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Chelyabinsk
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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Ryazan
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saint-Petersburg
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Russian Federation
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Samara
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Russian Federation
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St.Petersburg
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Spain
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Madrid
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Spain
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Barcelona
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Switzerland
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Bellinzona
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Switzerland
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Geneva
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Switzerland
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Zuerich
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Turkey
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Kadikoy
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Adana
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Ankara
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Antalya
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Edirne
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Konya
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United Kingdom
State/province [84] 0 0
Manchester
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03742895
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03742895