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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05609968




Registration number
NCT05609968
Ethics application status
Date submitted
2/11/2022
Date registered
8/11/2022
Date last updated
27/06/2024

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) Monotherapy Versus Sacituzumab Govitecan in Combination With Pembrolizumab for Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) =50% (MK-3475-D46)
Scientific title
An Open-label, Multicenter, Phase 3 Randomized, Active-Comparator-Controlled Clinical Study of Pembrolizumab (MK-3475) in Combination With Sacituzumab Govitecan Versus MK-3475 Monotherapy as First-line Treatment in Participants With PD L1 TPS Greater Than or Equal to 50% Metastatic Non-small Cell Lung Cancer (KEYNOTE D46/EVOKE-03)
Secondary ID [1] 0 0
MK-3475-D46
Secondary ID [2] 0 0
3475-D46
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

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

Experimental: Pembrolizumab + Sacituzumab Govitecan - Participants receive sacituzumab govitecan 10mg/kg intravenous (IV) infusion once weekly on Day 1 and Day 8 of a continuous 21-day cycle until progressive disease (PD) requiring discontinuation, unacceptable toxicity, withdrawal of consent, or death. Participants receive pembrolizumab 200mg IV infusion on Day 1 every 3 weeks (Q3W) for up to 35 cycles (each cycle length = 21 days).

Experimental: Pembrolizumab - Participants receive pembrolizumab 200mg IV infusion on Day 1 Q3W for up to 35 cycles (each cycle length = 21 days).


Treatment: Other: Sacituzumab Govitecan
IV infusion

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

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
Up to approximately 34 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 48 months
Secondary outcome [1] 0 0
Objective Response (OR)
Timepoint [1] 0 0
Up to approximately 34 months
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Up to approximately 48 months
Secondary outcome [3] 0 0
Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
Timepoint [3] 0 0
Baseline and up to approximately 48 months
Secondary outcome [4] 0 0
Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
Timepoint [4] 0 0
Baseline and up to approximately 48 months
Secondary outcome [5] 0 0
Change from Baseline in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30
Timepoint [5] 0 0
Baseline and up to approximately 48 months
Secondary outcome [6] 0 0
Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30
Timepoint [6] 0 0
Baseline and up to approximately 48 months
Secondary outcome [7] 0 0
Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC QLQ-LC13)
Timepoint [7] 0 0
Baseline and up to approximately 48 months
Secondary outcome [8] 0 0
Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
Timepoint [8] 0 0
Baseline and up to approximately 48 months
Secondary outcome [9] 0 0
Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30
Timepoint [9] 0 0
Up to approximately 48 months
Secondary outcome [10] 0 0
TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
Timepoint [10] 0 0
Up to approximately 48 months
Secondary outcome [11] 0 0
TTD in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30
Timepoint [11] 0 0
Up to approximately 48 months
Secondary outcome [12] 0 0
TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 11
Timepoint [12] 0 0
Up to approximately 48 months
Secondary outcome [13] 0 0
TTD in Cough Score (Item 31) on the EORTC QLQ-LC13
Timepoint [13] 0 0
Up to approximately 48 months
Secondary outcome [14] 0 0
TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
Timepoint [14] 0 0
Up to approximately 48 months
Secondary outcome [15] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [15] 0 0
Up to approximately 48 months
Secondary outcome [16] 0 0
Number of Participants Who Discontinue Study Treatment Due To an AE
Timepoint [16] 0 0
Up to approximately 48 months

Eligibility
Key inclusion criteria
The main inclusion criteria include but are not limited to the following:

* Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
* Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase 1 (ALK-1), or ROS proto-oncogene 1 (ROS-1)-directed therapy is not indicated as primary therapy
* Has provided tumor tissue that demonstrates PD-L1 tumor proportion score (TPS) =50% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory
* Has a life expectancy of at least 3 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The main exclusion criteria include but are not limited to the following:

* Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
* Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC
* Has previously received treatment with Topoisomerase 1 inhibitors or Trop-2 targeted therapy
* Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids
* Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study intervention
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration
* Has cardiac disease

* Myocardial infarction or unstable angina pectoris within 6 months of enrollment
* History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications; history of QT interval prolongation
* New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of <40%
* Has active chronic inflammatory bowel disease
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has severe hypersensitivity (=Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients
* Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* Has history of human immunodeficiency virus (HIV) infection
* History of hepatitis B or known active hepatitis C virus infection
* Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Have not adequately recovered from major surgery or have ongoing surgical complications

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/08/2028
Actual
Sample size
Target
614
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Orange Hospital-Clinical Trials Unit ( Site 0600) - Orange
Recruitment hospital [2] 0 0
Cancer Research SA-St Andrews Hospital ( Site 0603) - Adelaide
Recruitment hospital [3] 0 0
Frankston Hospital-Oncology and Haematology ( Site 0601) - Frankston
Recruitment postcode(s) [1] 0 0
2800 - Orange
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3199 - Frankston
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
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New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
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Texas
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Brazil
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Ceara
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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British Columbia
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Canada
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Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
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Chile
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Region M. De Santiago
Country [17] 0 0
China
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Anhui
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China
State/province [18] 0 0
Beijing
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China
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Chongqing
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China
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Fujian
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Guangdong
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China
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Guangxi
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China
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Heilongjiang
Country [24] 0 0
China
State/province [24] 0 0
Henan
Country [25] 0 0
China
State/province [25] 0 0
Hubei
Country [26] 0 0
China
State/province [26] 0 0
Hunan
Country [27] 0 0
China
State/province [27] 0 0
Jiangsu
Country [28] 0 0
China
State/province [28] 0 0
Jiangxi
Country [29] 0 0
China
State/province [29] 0 0
Jilin
Country [30] 0 0
China
State/province [30] 0 0
Shaanxi
Country [31] 0 0
China
State/province [31] 0 0
Shandong
Country [32] 0 0
China
State/province [32] 0 0
Shanghai
Country [33] 0 0
China
State/province [33] 0 0
Sichuan
Country [34] 0 0
China
State/province [34] 0 0
Zhejiang
Country [35] 0 0
Estonia
State/province [35] 0 0
Harjumaa
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Estonia
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Tartumaa
Country [37] 0 0
Germany
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Baden-Wurttemberg
Country [38] 0 0
Germany
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Bayern
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Germany
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Rheinland-Pfalz
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Germany
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Sachsen-Anhalt
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Germany
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Berlin
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Greece
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Attiki
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Greece
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Thessaloniki
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Israel
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Jerusalem
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Israel
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KfarSaba
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Israel
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Petah Tikva
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Israel
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Tel Aviv
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Israel
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Zerifin
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Napoli
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Italy
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Toscana
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Italy
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Verona
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Italy
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Parma
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Japan
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Aichi
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Fukuoka
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Miyagi
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Niigata
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Okayama
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Osaka
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Saitama
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Japan
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Shizuoka
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Tokyo
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Japan
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Wakayama
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Korea, Republic of
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Jeonranamdo
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Korea, Republic of
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Kyongsangnam-do
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Korea, Republic of
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Taejon-Kwangyokshi
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Korea, Republic of
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Seoul
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Latvia
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Daugavpils Novads
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Liepaja
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Riga
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Lithuania
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Kauno Apskritis
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Lithuania
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Vilniaus Miestas
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Kelantan
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Pulau Pinang
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Selangor
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Peru
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Ariqipa
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Peru
State/province [82] 0 0
Junin
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Peru
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La Libertad
Country [84] 0 0
Peru
State/province [84] 0 0
Lima
Country [85] 0 0
Philippines
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Davao Del Sur
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Philippines
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National Capital Region
Country [87] 0 0
Philippines
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Cebu
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Poland
State/province [88] 0 0
Kujawsko-pomorskie
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Poland
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Mazowieckie
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Poland
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Podkarpackie
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Poland
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Pomorskie
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Poland
State/province [92] 0 0
Slaskie
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Poland
State/province [93] 0 0
Wielkopolskie
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Romania
State/province [94] 0 0
Bucuresti
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Romania
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Cluj
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Romania
State/province [96] 0 0
Dolj
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Romania
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Timis
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
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Kaohsiung
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Taiwan
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Tainan
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Taiwan
State/province [102] 0 0
Taoyuan
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Thailand
State/province [103] 0 0
Chiang Mai
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Thailand
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Krung Thep Maha Nakhon
Country [105] 0 0
Thailand
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Lampang
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Thailand
State/province [106] 0 0
Songkhla
Country [107] 0 0
Thailand
State/province [107] 0 0
Ubon Ratchathani
Country [108] 0 0
Turkey
State/province [108] 0 0
Ankara
Country [109] 0 0
Turkey
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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
Country [112] 0 0
Turkey
State/province [112] 0 0
Mersin
Country [113] 0 0
United Kingdom
State/province [113] 0 0
England
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Leicestershire
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
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Gilead Sciences
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare pembrolizumab (MK-3475) in combination with sacituzumab govitecan with pembrolizumab alone with respect to progression-free survival (PFS) and overall survival (OS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) among adults with metastatic non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) =50%).
Trial website
https://clinicaltrials.gov/study/NCT05609968
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
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/study/NCT05609968