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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03976362




Registration number
NCT03976362
Ethics application status
Date submitted
3/06/2019
Date registered
6/06/2019
Date last updated
5/04/2024

Titles & IDs
Public title
A Study of Pembrolizumab (MK-3475) With or Without Maintenance Olaparib in First-line Metastatic Squamous Non-small Cell Lung Cancer (NSCLC, MK-7339-008/KEYLYNK-008)
Scientific title
A Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance Olaparib in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
MK-7339-008
Secondary ID [2] 0 0
7339-008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Squamous Cell, Non-small-cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Carboplatin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Olaparib
Treatment: Drugs - Placebo

Experimental: Pembrolizumab + Carboplatin + Taxane + Olaparib - For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). 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 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 centrally verified progressive disease, physician decision or intolerable toxicity.

Active Comparator: Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo - For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). 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 for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.


Other interventions: Pembrolizumab
IV infusion

Treatment: Drugs: Carboplatin
IV infusion

Treatment: Drugs: Paclitaxel
IV infusion

Treatment: Drugs: Nab-paclitaxel
IV infusion

Treatment: Drugs: Olaparib
Tablets

Treatment: Drugs: Placebo
Placebo to olaparib, tablets
Intervention code [1] 0 0
Other interventions
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 4 years
Secondary outcome [1] 0 0
Number of Participants With One or More Adverse Events (AEs)
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
Number of participants discontinuing study intervention due to adverse events (AEs)
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 European Organization for Research and Treatment of Cancer (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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 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 [8] 0 0
Up to approximately 5 years
Secondary outcome [9] 0 0
Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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 European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (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 squamous NSCLC.

2. Have Stage IV squamous NSCLC.

3. Have measurable disease based on RECIST 1.1.

4. Have not received prior systemic treatment for their advanced/metastatic NSCLC.

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 receive study intervention(s).
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 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

7. Have a life expectancy of at least 3 months.

8. Has adequate organ function.

9. 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.

10. Male participants must refrain from donating sperm 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 non-squamous 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 metastases and/or carcinomatous meningitis.

4. Has a known hypersensitivity to any components or excipients of carboplatin,
paclitaxel or nab-paclitaxel, or olaparib.

5. Has a severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its
excipients.

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.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
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
12/03/2025
Actual
Sample size
Target
Accrual to date
Final
591
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
Nova Scotia
Country [31] 0 0
Canada
State/province [31] 0 0
Ontario
Country [32] 0 0
Canada
State/province [32] 0 0
Quebec
Country [33] 0 0
France
State/province [33] 0 0
Aisne
Country [34] 0 0
France
State/province [34] 0 0
Calvados
Country [35] 0 0
France
State/province [35] 0 0
Maine-et-Loire
Country [36] 0 0
France
State/province [36] 0 0
Meurthe-et-Moselle
Country [37] 0 0
France
State/province [37] 0 0
Moselle
Country [38] 0 0
France
State/province [38] 0 0
Puy-de-Dome
Country [39] 0 0
France
State/province [39] 0 0
Pyrenees-Atlantiques
Country [40] 0 0
France
State/province [40] 0 0
Seine-Maritime
Country [41] 0 0
France
State/province [41] 0 0
Val-de-Marne
Country [42] 0 0
Germany
State/province [42] 0 0
Bayern
Country [43] 0 0
Germany
State/province [43] 0 0
Hessen
Country [44] 0 0
Germany
State/province [44] 0 0
Niedersachsen
Country [45] 0 0
Germany
State/province [45] 0 0
Nordrhein-Westfalen
Country [46] 0 0
Germany
State/province [46] 0 0
Rheinland-Pfalz
Country [47] 0 0
Germany
State/province [47] 0 0
Thuringen
Country [48] 0 0
Germany
State/province [48] 0 0
Hamburg
Country [49] 0 0
Japan
State/province [49] 0 0
Aichi
Country [50] 0 0
Japan
State/province [50] 0 0
Chiba
Country [51] 0 0
Japan
State/province [51] 0 0
Fukuoka
Country [52] 0 0
Japan
State/province [52] 0 0
Ishikawa
Country [53] 0 0
Japan
State/province [53] 0 0
Kanagawa
Country [54] 0 0
Japan
State/province [54] 0 0
Miyagi
Country [55] 0 0
Japan
State/province [55] 0 0
Osaka
Country [56] 0 0
Japan
State/province [56] 0 0
Shizuoka
Country [57] 0 0
Japan
State/province [57] 0 0
Niigata
Country [58] 0 0
Japan
State/province [58] 0 0
Okayama
Country [59] 0 0
Japan
State/province [59] 0 0
Tokyo
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Chungbuk
Country [61] 0 0
Korea, Republic of
State/province [61] 0 0
Kyonggi-do
Country [62] 0 0
Korea, Republic of
State/province [62] 0 0
Kyongsangnam-do
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Seoul
Country [64] 0 0
Mexico
State/province [64] 0 0
Baja California Sur
Country [65] 0 0
Mexico
State/province [65] 0 0
Jalisco
Country [66] 0 0
Mexico
State/province [66] 0 0
Nuevo Leon
Country [67] 0 0
Mexico
State/province [67] 0 0
Veracruz
Country [68] 0 0
Mexico
State/province [68] 0 0
Cdmx
Country [69] 0 0
New Zealand
State/province [69] 0 0
Manawatu-Wanganui
Country [70] 0 0
New Zealand
State/province [70] 0 0
Wellington
Country [71] 0 0
Poland
State/province [71] 0 0
Dolnoslaskie
Country [72] 0 0
Poland
State/province [72] 0 0
Malopolskie
Country [73] 0 0
Poland
State/province [73] 0 0
Mazowieckie
Country [74] 0 0
Poland
State/province [74] 0 0
Slaskie
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
Bucuresti
Country [80] 0 0
Romania
State/province [80] 0 0
Constanta
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Moskovskaya Oblast
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Moskva
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Nizhegorodskaya Oblast
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Omskaya Oblast
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Samarskaya Oblast
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Sankt-Peterburg
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Tatarstan, Respublika
Country [88] 0 0
Spain
State/province [88] 0 0
Barcelona
Country [89] 0 0
Spain
State/province [89] 0 0
La Coruna
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Malaga
Country [92] 0 0
Spain
State/province [92] 0 0
Sevilla
Country [93] 0 0
Taiwan
State/province [93] 0 0
Kaohsiung
Country [94] 0 0
Taiwan
State/province [94] 0 0
Taichung
Country [95] 0 0
Taiwan
State/province [95] 0 0
Tainan
Country [96] 0 0
Taiwan
State/province [96] 0 0
Taipei
Country [97] 0 0
Taiwan
State/province [97] 0 0
Taoyuan
Country [98] 0 0
Turkey
State/province [98] 0 0
Tekirdas
Country [99] 0 0
Turkey
State/province [99] 0 0
Adana
Country [100] 0 0
Turkey
State/province [100] 0 0
Ankara
Country [101] 0 0
Turkey
State/province [101] 0 0
Istanbul
Country [102] 0 0
Turkey
State/province [102] 0 0
Izmir
Country [103] 0 0
Turkey
State/province [103] 0 0
Kayseri
Country [104] 0 0
Turkey
State/province [104] 0 0
Samsun
Country [105] 0 0
Ukraine
State/province [105] 0 0
Cherkaska Oblast
Country [106] 0 0
Ukraine
State/province [106] 0 0
Dnipropetrovska Oblast
Country [107] 0 0
Ukraine
State/province [107] 0 0
Ivano-Frankivska Oblast
Country [108] 0 0
Ukraine
State/province [108] 0 0
Kharkivska Oblast
Country [109] 0 0
Ukraine
State/province [109] 0 0
Kirovohradska Oblast
Country [110] 0 0
Ukraine
State/province [110] 0 0
Kyivska Oblast
Country [111] 0 0
Ukraine
State/province [111] 0 0
Odeska Oblast
Country [112] 0 0
Ukraine
State/province [112] 0 0
Zakarpatska Oblast
Country [113] 0 0
Ukraine
State/province [113] 0 0
Kyiv
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Essex
Country [115] 0 0
United Kingdom
State/province [115] 0 0
London, City Of
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Newcastle Upon Tyne
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Suffolk
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Wales
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Worcestershire
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Birmingham
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Edinburg

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 olaparib placebo for the treatment of squamous NSCLC. The
study's 2 primary hypotheses are:

1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance
olaparib placebo with respect to progression-free survival (PFS) per RECIST 1.1 by
blinded independent clinical review (BICR).

2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance
olaparib placebo with respect to overall survival (OS).

As of Amendment 07, there will be no further analyses for OS and patient-reported outcome
assessments.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03976362
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/ct2/show/NCT03976362