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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04123366




Registration number
NCT04123366
Ethics application status
Date submitted
9/10/2019
Date registered
10/10/2019

Titles & IDs
Public title
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)
Scientific title
A Phase 2 Study of Olaparib in Combination With Pembrolizumab in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer
Secondary ID [1] 0 0
MK-7339-007
Secondary ID [2] 0 0
7339-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

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

Experimental: Olaparib+Pembrolizumab - Participants receive olaparib 300 mg via oral tablet 2 times each day PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 21-day cycle. Participants may receive olaparib+pembrolizumab for up to approximately 2 years.


Treatment: Drugs: Olaparib
Oral tablet

Treatment: Other: Pembrolizumab
Intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 in Biomarker Subgroups
Timepoint [1] 0 0
Up to ~3 years
Secondary outcome [1] 0 0
Duration of Response (DOR) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups
Timepoint [1] 0 0
Up to ~3 years
Secondary outcome [2] 0 0
Progression-Free Survival (PFS) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups
Timepoint [2] 0 0
Up to ~3 years
Secondary outcome [3] 0 0
Overall Survival (OS) in Biomarker Subgroups
Timepoint [3] 0 0
Up to ~3 years
Secondary outcome [4] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [4] 0 0
Up to ~3 years
Secondary outcome [5] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [5] 0 0
Up to ~3 years
Secondary outcome [6] 0 0
Objective Response Rate (ORR) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations
Timepoint [6] 0 0
Up to ~3 years
Secondary outcome [7] 0 0
Duration of Response (DOR) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations
Timepoint [7] 0 0
Up to ~3 years
Secondary outcome [8] 0 0
Progression-Free Survival (PFS) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations
Timepoint [8] 0 0
Up to ~3 years
Secondary outcome [9] 0 0
Overall Survival (OS) in Additional Biomarker Subpopulations
Timepoint [9] 0 0
Up to ~3 years
Secondary outcome [10] 0 0
Number of Participants with Cancer Antigen-125 (CA-125) Level of =2 × Upper Limit of Normal (ULN) Among Participants with Ovarian Cancer
Timepoint [10] 0 0
Up to ~3 years
Secondary outcome [11] 0 0
Number of Participants with Cancer Antigen-125 (CA-125) Level =2 × Nadir (Lowest) Value Among Participants with Ovarian Cancer Who Had Elevated CA-125 Levels =ULN at Baseline
Timepoint [11] 0 0
Up to ~3 years
Secondary outcome [12] 0 0
Number of Participants with a Change from Baseline in Prostate-Specific Antigen (PSA) Level of =50% Among Participants with Prostate Cancer
Timepoint [12] 0 0
Up to ~3 years

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 =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
Minimum age
18 Years
Maximum age
No limit
Sex
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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
24/07/2025
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital ( Site 2202) - Blacktown
Recruitment hospital [2] 0 0
Tasman Oncology Research Pty Ltd ( Site 2203) - Southport
Recruitment hospital [3] 0 0
Monash Medical Centre ( Site 2205) - Clayton
Recruitment hospital [4] 0 0
Linear Clinical Research Ltd ( Site 2206) - Nedlands
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Argentina
State/province [16] 0 0
Caba
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Argentina
State/province [18] 0 0
La Rioja
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
New Brunswick
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Colombia
State/province [22] 0 0
Antioquia
Country [23] 0 0
Colombia
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Atlantico
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Colombia
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Santander
Country [25] 0 0
Colombia
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Valle Del Cauca
Country [26] 0 0
France
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Doubs
Country [27] 0 0
France
State/province [27] 0 0
Herault
Country [28] 0 0
France
State/province [28] 0 0
Seine-Maritime
Country [29] 0 0
France
State/province [29] 0 0
Val-de-Marne
Country [30] 0 0
France
State/province [30] 0 0
Vendee
Country [31] 0 0
Germany
State/province [31] 0 0
Bayern
Country [32] 0 0
Germany
State/province [32] 0 0
Nordrhein-Westfalen
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Guatemala
State/province [34] 0 0
Guatemala
Country [35] 0 0
Guatemala
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Quetzaltenango
Country [36] 0 0
Israel
State/province [36] 0 0
Haifa
Country [37] 0 0
Israel
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Jerusalem
Country [38] 0 0
Israel
State/province [38] 0 0
Kfar Saba
Country [39] 0 0
Israel
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Petah Tikva
Country [40] 0 0
Israel
State/province [40] 0 0
Ramat Gan
Country [41] 0 0
Israel
State/province [41] 0 0
Tel Aviv
Country [42] 0 0
Italy
State/province [42] 0 0
Emilia-Romagna
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Napoli
Country [45] 0 0
Italy
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Siena
Country [46] 0 0
Japan
State/province [46] 0 0
Aichi
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Japan
State/province [47] 0 0
Chiba
Country [48] 0 0
Japan
State/province [48] 0 0
Hokkaido
Country [49] 0 0
Japan
State/province [49] 0 0
Fukuoka
Country [50] 0 0
Japan
State/province [50] 0 0
Okayama
Country [51] 0 0
Japan
State/province [51] 0 0
Tokyo
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Kyonggi-do
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Seoul
Country [54] 0 0
Latvia
State/province [54] 0 0
Daugavpils
Country [55] 0 0
Latvia
State/province [55] 0 0
Liepaja
Country [56] 0 0
Latvia
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Riga
Country [57] 0 0
Mexico
State/province [57] 0 0
Guanajuato
Country [58] 0 0
Mexico
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Nuevo Leon
Country [59] 0 0
Mexico
State/province [59] 0 0
Queretaro
Country [60] 0 0
Mexico
State/province [60] 0 0
Tamaulipas
Country [61] 0 0
Mexico
State/province [61] 0 0
Ciudad de Mexico
Country [62] 0 0
Mexico
State/province [62] 0 0
Puebla
Country [63] 0 0
Peru
State/province [63] 0 0
Ariqipa
Country [64] 0 0
Peru
State/province [64] 0 0
Qallaw
Country [65] 0 0
Peru
State/province [65] 0 0
Qusqu
Country [66] 0 0
Peru
State/province [66] 0 0
Lima
Country [67] 0 0
Poland
State/province [67] 0 0
Mazowieckie
Country [68] 0 0
Poland
State/province [68] 0 0
Pomorskie
Country [69] 0 0
Puerto Rico
State/province [69] 0 0
Manati
Country [70] 0 0
Puerto Rico
State/province [70] 0 0
Ponce
Country [71] 0 0
Puerto Rico
State/province [71] 0 0
Rio Piedras
Country [72] 0 0
Puerto Rico
State/province [72] 0 0
San Juan
Country [73] 0 0
Romania
State/province [73] 0 0
Alba
Country [74] 0 0
Romania
State/province [74] 0 0
Cluj
Country [75] 0 0
Romania
State/province [75] 0 0
Dolj
Country [76] 0 0
Romania
State/province [76] 0 0
Timis
Country [77] 0 0
South Africa
State/province [77] 0 0
Free State
Country [78] 0 0
South Africa
State/province [78] 0 0
Gauteng
Country [79] 0 0
South Africa
State/province [79] 0 0
Kwazulu-Natal
Country [80] 0 0
South Africa
State/province [80] 0 0
Western Cape
Country [81] 0 0
Spain
State/province [81] 0 0
Madrid
Country [82] 0 0
Spain
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Barcelona
Country [83] 0 0
Sweden
State/province [83] 0 0
Skane Lan
Country [84] 0 0
Sweden
State/province [84] 0 0
Stockholms Lan
Country [85] 0 0
Sweden
State/province [85] 0 0
Uppsala Lan
Country [86] 0 0
Turkey
State/province [86] 0 0
Adana
Country [87] 0 0
Turkey
State/province [87] 0 0
Ankara
Country [88] 0 0
Turkey
State/province [88] 0 0
Antalya
Country [89] 0 0
Turkey
State/province [89] 0 0
Edirne
Country [90] 0 0
Turkey
State/province [90] 0 0
Istanbul
Country [91] 0 0
Turkey
State/province [91] 0 0
Izmir
Country [92] 0 0
Turkey
State/province [92] 0 0
Konya
Country [93] 0 0
Turkey
State/province [93] 0 0
Malatya
Country [94] 0 0
Ukraine
State/province [94] 0 0
Cherkaska Oblast
Country [95] 0 0
Ukraine
State/province [95] 0 0
Dnipropetrovska Oblast
Country [96] 0 0
Ukraine
State/province [96] 0 0
Ivano-Frankivska Oblast
Country [97] 0 0
Ukraine
State/province [97] 0 0
Kharkivska Oblast
Country [98] 0 0
Ukraine
State/province [98] 0 0
Khmelnytska Oblast
Country [99] 0 0
Ukraine
State/province [99] 0 0
Kirovohradska Oblast
Country [100] 0 0
Ukraine
State/province [100] 0 0
Kyivska Oblast
Country [101] 0 0
Ukraine
State/province [101] 0 0
Vinnytska Oblast
Country [102] 0 0
Ukraine
State/province [102] 0 0
Zaporizka Oblast
Country [103] 0 0
Ukraine
State/province [103] 0 0
Zhytomyrska Oblast

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04123366