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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03515837




Registration number
NCT03515837
Ethics application status
Date submitted
23/04/2018
Date registered
4/05/2018

Titles & IDs
Public title
Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With Tyrosine Kinase Inhibitor- (TKI)-Resistant Epidermal Growth Factor Receptor- (EGFR)-Mutated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-789/KEYNOTE-789)
Scientific title
A Randomized, Double-Blind, Phase 3 Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Participants (KEYNOTE-789)
Secondary ID [1] 0 0
MK-3475-789
Secondary ID [2] 0 0
3475-789
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 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 - saline solution

Experimental: Pembro+Pemetrexed+Chemo - Participants receive pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve \[AUC\] 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]).

Active comparator: Placebo+Pemetrexed+Chemo - Participants receive normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]).


Treatment: Other: pembrolizumab
IV infusion

Treatment: Drugs: pemetrexed
IV infusion

Treatment: Drugs: carboplatin
IV infusion

Treatment: Drugs: cisplatin
IV infusion

Treatment: Drugs: saline solution
IV infusion
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 ~40 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to ~51 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per RECIST 1.1
Timepoint [1] 0 0
Up to ~51 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per RECIST 1.1
Timepoint [2] 0 0
Up to ~51 months
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 (Item 29) and Quality of Life (Item 30) Combined Score
Timepoint [3] 0 0
Baseline and Week 18
Secondary outcome [4] 0 0
Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea
Timepoint [4] 0 0
Baseline and up to ~51 months
Secondary outcome [5] 0 0
Percentage of Participants Who Experienced an Adverse Event (AE)
Timepoint [5] 0 0
Up to ~44 months
Secondary outcome [6] 0 0
Percentage of Participants Who Discontinued Study Treatment Due to AEs
Timepoint [6] 0 0
Up to ~41 months

Eligibility
Key inclusion criteria
* Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC.
* Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R.
* Investigator-determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation; b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment; c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status. Note: TKI washout period for all participants is 1 week or 2 half-lives after last treatment dose, whichever is longer. TKI washout should be completed prior to first dose of study treatment.
* Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
* Provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated.
* Life expectancy of at least 3 months.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization.
* Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents.
* Female participants must not be pregnant, not breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.
* Adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible.
* Symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
* Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or 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, CD137).
* Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC. [Notes: 1) Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. 2) If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3) Prior exposure to traditional medicine(s) is allowed as long as therapy was discontinued at least 4 weeks prior to the first dose of study treatment.]
* Received prior radiotherapy within 2 weeks of start of study treatment or has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
* Received a live vaccine within 30 days prior to the first dose of study treatment.
* Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
* Known additional malignancy that is progressing or has required active treatment within the past 5 years. (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.)
* Known active untreated CNS metastases and/or carcinomatous meningitis.
* Severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients.
* Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed.
* Active autoimmune disease that has required systemic treatment in past 2 years.
* History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Active infection requiring systemic therapy.
* Known history of human immunodeficiency virus (HIV) infection.
* Known history of Hepatitis B or known active Hepatitis C virus.
* Known history of active tuberculosis (TB; Bacillus tuberculosis)
* Pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.

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 administering 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/10/2023
Sample size
Target
Accrual to date
Final
492
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 0200) - Camperdown
Recruitment hospital [2] 0 0
Westmead Hospital ( Site 0201) - Westmead
Recruitment hospital [3] 0 0
Eastern Health ( Site 0202) - Box Hill
Recruitment hospital [4] 0 0
Austin Health ( Site 0203) - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Brazil
State/province [12] 0 0
Rio Grande Do Norte
Country [13] 0 0
Brazil
State/province [13] 0 0
Rio Grande Do Sul
Country [14] 0 0
Brazil
State/province [14] 0 0
Sao Paulo
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
China
State/province [17] 0 0
Anhui
Country [18] 0 0
China
State/province [18] 0 0
Beijing
Country [19] 0 0
China
State/province [19] 0 0
Chongqing
Country [20] 0 0
China
State/province [20] 0 0
Fujian
Country [21] 0 0
China
State/province [21] 0 0
Heilongjiang
Country [22] 0 0
China
State/province [22] 0 0
Henan
Country [23] 0 0
China
State/province [23] 0 0
Hunan
Country [24] 0 0
China
State/province [24] 0 0
Jiangsu
Country [25] 0 0
China
State/province [25] 0 0
Jilin
Country [26] 0 0
China
State/province [26] 0 0
Shanghai
Country [27] 0 0
China
State/province [27] 0 0
Shanxi
Country [28] 0 0
China
State/province [28] 0 0
Xinjiang
Country [29] 0 0
China
State/province [29] 0 0
Zhejiang
Country [30] 0 0
France
State/province [30] 0 0
Auvergne
Country [31] 0 0
France
State/province [31] 0 0
Calvados
Country [32] 0 0
France
State/province [32] 0 0
Cote-d'Or
Country [33] 0 0
France
State/province [33] 0 0
Doubs
Country [34] 0 0
France
State/province [34] 0 0
Hauts-de-Seine
Country [35] 0 0
France
State/province [35] 0 0
Indre-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
Sarthe
Country [38] 0 0
France
State/province [38] 0 0
Vienne
Country [39] 0 0
Germany
State/province [39] 0 0
Baden-Wurttemberg
Country [40] 0 0
Germany
State/province [40] 0 0
Bayern
Country [41] 0 0
Germany
State/province [41] 0 0
Niedersachsen
Country [42] 0 0
Germany
State/province [42] 0 0
Nordrhein-Westfalen
Country [43] 0 0
Germany
State/province [43] 0 0
Sachsen
Country [44] 0 0
Germany
State/province [44] 0 0
Hamburg
Country [45] 0 0
Hong Kong
State/province [45] 0 0
Hong Kong
Country [46] 0 0
Hong Kong
State/province [46] 0 0
Kowloon
Country [47] 0 0
Hong Kong
State/province [47] 0 0
Tuen Mun
Country [48] 0 0
Israel
State/province [48] 0 0
HaDarom
Country [49] 0 0
Israel
State/province [49] 0 0
HaMerkaz
Country [50] 0 0
Israel
State/province [50] 0 0
HaTsafon
Country [51] 0 0
Israel
State/province [51] 0 0
Heifa
Country [52] 0 0
Israel
State/province [52] 0 0
Tell Abib
Country [53] 0 0
Italy
State/province [53] 0 0
Lombardia
Country [54] 0 0
Italy
State/province [54] 0 0
Messina
Country [55] 0 0
Italy
State/province [55] 0 0
Torino
Country [56] 0 0
Italy
State/province [56] 0 0
Bari
Country [57] 0 0
Italy
State/province [57] 0 0
Firenze
Country [58] 0 0
Italy
State/province [58] 0 0
Napoli
Country [59] 0 0
Italy
State/province [59] 0 0
Roma
Country [60] 0 0
Japan
State/province [60] 0 0
Aichi
Country [61] 0 0
Japan
State/province [61] 0 0
Chiba
Country [62] 0 0
Japan
State/province [62] 0 0
Ehime
Country [63] 0 0
Japan
State/province [63] 0 0
Hyogo
Country [64] 0 0
Japan
State/province [64] 0 0
Ishikawa
Country [65] 0 0
Japan
State/province [65] 0 0
Kanagawa
Country [66] 0 0
Japan
State/province [66] 0 0
Osaka
Country [67] 0 0
Japan
State/province [67] 0 0
Shizuoka
Country [68] 0 0
Japan
State/province [68] 0 0
Fukuoka
Country [69] 0 0
Japan
State/province [69] 0 0
Niigata
Country [70] 0 0
Japan
State/province [70] 0 0
Okayama
Country [71] 0 0
Japan
State/province [71] 0 0
Tokyo
Country [72] 0 0
Japan
State/province [72] 0 0
Wakayama
Country [73] 0 0
Korea, Republic of
State/province [73] 0 0
Chungcheongbuk-do [Chungbuk]
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Incheon-gwangyeoksi [Incheon]
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Kyonggi-do
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Seoul-teukbyeolsi [Seoul]
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Ulsan-Kwangyokshi
Country [78] 0 0
Mexico
State/province [78] 0 0
Jalisco
Country [79] 0 0
Mexico
State/province [79] 0 0
Mexico City
Country [80] 0 0
Mexico
State/province [80] 0 0
Oaxaca
Country [81] 0 0
Mexico
State/province [81] 0 0
Tlalpan
Country [82] 0 0
Spain
State/province [82] 0 0
Barcelona [Barcelona]
Country [83] 0 0
Spain
State/province [83] 0 0
Madrid
Country [84] 0 0
Spain
State/province [84] 0 0
Malaga
Country [85] 0 0
Spain
State/province [85] 0 0
Sevilla
Country [86] 0 0
Sweden
State/province [86] 0 0
Ostergotlands Lan [se-05]
Country [87] 0 0
Sweden
State/province [87] 0 0
Skane Lan [se-12]
Country [88] 0 0
Sweden
State/province [88] 0 0
Stockholms Lan [se-01]
Country [89] 0 0
Sweden
State/province [89] 0 0
Vastra Gotalands Lan [se-14]
Country [90] 0 0
Taiwan
State/province [90] 0 0
New Taipei
Country [91] 0 0
Taiwan
State/province [91] 0 0
Changhua
Country [92] 0 0
Taiwan
State/province [92] 0 0
Hsinchu
Country [93] 0 0
Taiwan
State/province [93] 0 0
Hualien
Country [94] 0 0
Taiwan
State/province [94] 0 0
Kaohsiung
Country [95] 0 0
Taiwan
State/province [95] 0 0
Taichung
Country [96] 0 0
Taiwan
State/province [96] 0 0
Tainan
Country [97] 0 0
Taiwan
State/province [97] 0 0
Taipei
Country [98] 0 0
Taiwan
State/province [98] 0 0
Taoyuan
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Brighton And Hove
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Edinburgh, City Of
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Leicestershire
Country [102] 0 0
United Kingdom
State/province [102] 0 0
London, City Of
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Birmingham
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Leeds
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Romford

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?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Yang JC, Lee DH, Lee JS, Fan Y, de Marinis F, Iwam... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03515837