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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03976323




Registration number
NCT03976323
Ethics application status
Date submitted
3/06/2019
Date registered
6/06/2019
Date last updated
19/11/2024

Titles & IDs
Public title
Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)
Scientific title
A Phase 3 Study of Pembrolizumab in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Followed by Pembrolizumab and Maintenance Olaparib vs Maintenance Pemetrexed in the First-Line Treatment of Participants With Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
MK-7339-006
Secondary ID [2] 0 0
7339-006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Nonsquamous Non-small-cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

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

Experimental: Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib - For the Induction Phase, participants receive 4 cycles:

Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m\^2 IV on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4).

If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.

For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21-day cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until progressive disease, physician decision or intolerable toxicity.

Active comparator: Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed - For the Induction Phase, participants receive 4 cycles:

Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m\^2 IV on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21 day-cycle for up to 31 cycles PLUS maintenance pemetrexed IV 500 mg/m\^2 on Day 1 of each 21-day cycle. In the Maintenance Phase, the participant continues to receive maintenance pemetrexed until progressive disease, physician decision or intolerable toxicity.


Treatment: Other: Pembrolizumab
IV infusion

Treatment: Drugs: Pemetrexed
IV infusion

Treatment: Drugs: Carboplatin
IV infusion

Treatment: Drugs: Cisplatin
IV infusion

Treatment: Drugs: Olaparib
Tablets
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 3 years
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
Number of Participants Experiencing an Adverse Event (AE)
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
Number of Participants Discontinuing Study Treatment Due to Adverse Event (AE)
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [3] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 and 30) Scale Score
Timepoint [3] 0 0
Baseline (at randomization) and Week 18 post-randomization
Secondary outcome [4] 0 0
Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score
Timepoint [4] 0 0
Baseline (at randomization) and Week 18 post-randomization
Secondary outcome [5] 0 0
Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score
Timepoint [5] 0 0
Baseline (at randomization) and Week 18 post-randomization
Secondary outcome [6] 0 0
Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
Timepoint [6] 0 0
Baseline (at randomization) and Week 18 post-randomization
Secondary outcome [7] 0 0
Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score
Timepoint [7] 0 0
Baseline (at randomization) and Week 18 post-randomization
Secondary outcome [8] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score
Timepoint [8] 0 0
Up to approximately 5 years
Secondary outcome [9] 0 0
Time to True Deterioration (TTD) in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score
Timepoint [9] 0 0
Up to approximately 5 years
Secondary outcome [10] 0 0
Time to True Deterioration (TTD) in EORTC (QLQ-LC13 Chest Pain (Item 10) Scale Score
Timepoint [10] 0 0
Up to approximately 5 years
Secondary outcome [11] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
Timepoint [11] 0 0
Up to approximately 5 years
Secondary outcome [12] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score
Timepoint [12] 0 0
Up to approximately 5 years

Eligibility
Key inclusion criteria
1. Have a histologically or cytologically confirmed diagnosis nonsquamous NSCLC.
2. Have stage IV nonsquamous NSCLC.
3. Have confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1)-directed therapy is not indicated.
4. Have measurable disease based on RECIST 1.1.
5. Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated.

Note: Adequacy of biopsy specimen for the above analyses must be confirmed by the central laboratory before the participant can start the induction phase. Submission of another tumor specimen may be required prior to enrolling the participant, if adequate tumor tissue was not provided the first time.
6. Have a life expectancy of at least 3 months.
7. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status assessed within 7 days prior to the administration of study intervention.
8. Have not received prior systemic treatment for their advanced/metastatic NSCLC.
9. Have adequate organ function.
10. Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for 180 days afterwards.
11. Male participants must refrain from donating sperm, and female participants must refrain from donating eggs to others or freeze/store for her own use during the treatment period and for 180 days afterwards.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has predominantly squamous cell histology NSCLC.
2. Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment.
3. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
4. Has a severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
5. Has a known hypersensitivity to any components or excipients of cisplatin, carboplatin, pemetrexed, or olaparib.
6. Has an active autoimmune disease that has required systemic treatment in past 2 years.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
8. Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B infection, or known active hepatitis C virus infection.
9. Has interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment.
10. Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.
11. Has received prior therapy with an agent directed to programmed cell death ligand 1 (PD-L1), anti PD-L2, or directed to a stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
12. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
13. Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
14. Has completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 3
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
28/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
13/01/2025
Actual
Sample size
Target
Accrual to date
Final
672
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital ( Site 1201) - Liverpool
Recruitment hospital [2] 0 0
Southern Medical Day Care Centre ( Site 1200) - Wollongong
Recruitment hospital [3] 0 0
Townsville General Hospital ( Site 1202) - Townsville
Recruitment hospital [4] 0 0
Monash Cancer Centre ( Site 1205) - Clayton
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4814 - Townsville
Recruitment postcode(s) [4] 0 0
3168 - Clayton
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
Montana
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Caba
Country [17] 0 0
Argentina
State/province [17] 0 0
Cordoba
Country [18] 0 0
Argentina
State/province [18] 0 0
Santa Fe
Country [19] 0 0
Argentina
State/province [19] 0 0
Tucuman
Country [20] 0 0
Austria
State/province [20] 0 0
Oberosterreich
Country [21] 0 0
Austria
State/province [21] 0 0
Tirol
Country [22] 0 0
Austria
State/province [22] 0 0
Wien
Country [23] 0 0
Brazil
State/province [23] 0 0
Bahia
Country [24] 0 0
Brazil
State/province [24] 0 0
Ceara
Country [25] 0 0
Brazil
State/province [25] 0 0
Para
Country [26] 0 0
Brazil
State/province [26] 0 0
Rio Grande Do Sul
Country [27] 0 0
Brazil
State/province [27] 0 0
Santa Catarina
Country [28] 0 0
Brazil
State/province [28] 0 0
Sao Paulo
Country [29] 0 0
Brazil
State/province [29] 0 0
Rio de Janeiro
Country [30] 0 0
Canada
State/province [30] 0 0
British Columbia
Country [31] 0 0
Canada
State/province [31] 0 0
Nova Scotia
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
Colombia
State/province [34] 0 0
Antioquia
Country [35] 0 0
Colombia
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Atlantico
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Colombia
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Distrito Capital De Bogota
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France
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Aisne
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France
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Calvados
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France
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Maine-et-Loire
Country [40] 0 0
France
State/province [40] 0 0
Meurthe-et-Moselle
Country [41] 0 0
France
State/province [41] 0 0
Moselle
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France
State/province [42] 0 0
Puy-de-Dome
Country [43] 0 0
France
State/province [43] 0 0
Pyrenees-Atlantiques
Country [44] 0 0
France
State/province [44] 0 0
Seine-Maritime
Country [45] 0 0
France
State/province [45] 0 0
Val-de-Marne
Country [46] 0 0
Germany
State/province [46] 0 0
Bayern
Country [47] 0 0
Germany
State/province [47] 0 0
Hessen
Country [48] 0 0
Germany
State/province [48] 0 0
Niedersachsen
Country [49] 0 0
Germany
State/province [49] 0 0
Nordrhein-Westfalen
Country [50] 0 0
Germany
State/province [50] 0 0
Rheinland-Pfalz
Country [51] 0 0
Germany
State/province [51] 0 0
Thuringen
Country [52] 0 0
Germany
State/province [52] 0 0
Hamburg
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Japan
State/province [53] 0 0
Aichi
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Japan
State/province [54] 0 0
Chiba
Country [55] 0 0
Japan
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Ishikawa
Country [56] 0 0
Japan
State/province [56] 0 0
Kanagawa
Country [57] 0 0
Japan
State/province [57] 0 0
Miyagi
Country [58] 0 0
Japan
State/province [58] 0 0
Osaka
Country [59] 0 0
Japan
State/province [59] 0 0
Shizuoka
Country [60] 0 0
Japan
State/province [60] 0 0
Fukuoka
Country [61] 0 0
Japan
State/province [61] 0 0
Niigata
Country [62] 0 0
Japan
State/province [62] 0 0
Okayama
Country [63] 0 0
Japan
State/province [63] 0 0
Tokyo
Country [64] 0 0
Korea, Republic of
State/province [64] 0 0
Chungbuk
Country [65] 0 0
Korea, Republic of
State/province [65] 0 0
Kyonggi-do
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Kyongsangnam-do
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Seoul
Country [68] 0 0
New Zealand
State/province [68] 0 0
Manawatu-Wanganui
Country [69] 0 0
New Zealand
State/province [69] 0 0
Wellington
Country [70] 0 0
Poland
State/province [70] 0 0
Dolnoslaskie
Country [71] 0 0
Poland
State/province [71] 0 0
Malopolskie
Country [72] 0 0
Poland
State/province [72] 0 0
Mazowieckie
Country [73] 0 0
Poland
State/province [73] 0 0
Slaskie
Country [74] 0 0
Poland
State/province [74] 0 0
Warminsko-mazurskie
Country [75] 0 0
Poland
State/province [75] 0 0
Wielkopolskie
Country [76] 0 0
Romania
State/province [76] 0 0
Cluj
Country [77] 0 0
Romania
State/province [77] 0 0
Dolj
Country [78] 0 0
Romania
State/province [78] 0 0
Timis
Country [79] 0 0
Romania
State/province [79] 0 0
Brasov
Country [80] 0 0
Romania
State/province [80] 0 0
Bucuresti
Country [81] 0 0
Romania
State/province [81] 0 0
Constanta
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Leningradskaya Oblast
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Moskovskaya Oblast
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Moskva
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Nizhegorodskaya Oblast
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Omskaya Oblast
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Samarskaya Oblast
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Sankt-Peterburg
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Tatarstan, Respublika
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Valenciana, Comunitat
Country [92] 0 0
Spain
State/province [92] 0 0
Barcelona
Country [93] 0 0
Spain
State/province [93] 0 0
Sevilla
Country [94] 0 0
Spain
State/province [94] 0 0
Zaragoza
Country [95] 0 0
Taiwan
State/province [95] 0 0
Kaohsiung
Country [96] 0 0
Taiwan
State/province [96] 0 0
Taichung
Country [97] 0 0
Taiwan
State/province [97] 0 0
Tainan
Country [98] 0 0
Taiwan
State/province [98] 0 0
Taipei
Country [99] 0 0
Taiwan
State/province [99] 0 0
Taoyuan
Country [100] 0 0
Turkey
State/province [100] 0 0
Tekirdas
Country [101] 0 0
Turkey
State/province [101] 0 0
Adana
Country [102] 0 0
Turkey
State/province [102] 0 0
Ankara
Country [103] 0 0
Turkey
State/province [103] 0 0
Istanbul
Country [104] 0 0
Turkey
State/province [104] 0 0
Izmir
Country [105] 0 0
Turkey
State/province [105] 0 0
Kayseri
Country [106] 0 0
Turkey
State/province [106] 0 0
Samsun
Country [107] 0 0
Ukraine
State/province [107] 0 0
Cherkaska Oblast
Country [108] 0 0
Ukraine
State/province [108] 0 0
Dnipropetrovska Oblast
Country [109] 0 0
Ukraine
State/province [109] 0 0
Ivano-Frankivska Oblast
Country [110] 0 0
Ukraine
State/province [110] 0 0
Kharkivska Oblast
Country [111] 0 0
Ukraine
State/province [111] 0 0
Kirovohradska Oblast
Country [112] 0 0
Ukraine
State/province [112] 0 0
Kyivska Oblast
Country [113] 0 0
Ukraine
State/province [113] 0 0
Odeska Oblast
Country [114] 0 0
Ukraine
State/province [114] 0 0
Zakarpatska Oblast
Country [115] 0 0
Ukraine
State/province [115] 0 0
Kyiv
Country [116] 0 0
United Kingdom
State/province [116] 0 0
London, City Of
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Suffolk
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Worcestershire
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Birmingham
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Edinburg
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Swansea

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

Ethics approval
Ethics application status

Summary
Brief summary
The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs pembrolizumab plus maintenance pemetrexed for the treatment of nonsquamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) by blinded independent clinical review (BICR) and 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to overall survival (OS).
Trial website
https://clinicaltrials.gov/study/NCT03976323
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03976323