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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/NCT03425643




Registration number
NCT03425643
Ethics application status
Date submitted
2/02/2018
Date registered
7/02/2018
Date last updated
13/11/2023

Titles & IDs
Public title
Efficacy and Safety of Pembrolizumab (MK-3475) With Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (MK-3475-671/KEYNOTE-671)
Scientific title
A Phase III, Randomized, Double-blind Trial of Platinum Doublet Chemotherapy +/-Pembrolizumab (MK-3475) as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (NSCLC) (KEYNOTE-671)
Secondary ID [1] 0 0
MK-3475-671
Secondary ID [2] 0 0
3475-671
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
Other interventions - Pembrolizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Cisplatin
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Pemetrexed

Experimental: NAC + Neoadjuvant/Adjuvant Pembrolizumab - Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, intravenous (IV); given on cycle day 1] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1].
Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, IV; given on cycle day 1].

Placebo Comparator: NAC + Neoadjuvant/Adjuvant Placebo - Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1] in combination with platinum doublet NAC, consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1].
Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1].


Other interventions: Pembrolizumab
200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.

Treatment: Drugs: Placebo
Normal saline by IV infusion Q3W, given on cycle day 1.

Treatment: Drugs: Cisplatin
75 mg/m^2 by IV infusion Q3W, given on cycle day 1.

Treatment: Drugs: Gemcitabine
1000 mg/m^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC.

Treatment: Drugs: Pemetrexed
500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.
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
Event Free Survival (EFS)
Timepoint [1] 0 0
Up to approximately 5 years
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
Major Pathological Response (mPR) Rate
Timepoint [1] 0 0
Up to approximately 7 weeks following completion of neoadjuvant treatment (up to Study Week 20)
Secondary outcome [2] 0 0
Pathological Complete Response (pCR) Rate
Timepoint [2] 0 0
Up to approximately 7 weeks following completion of neoadjuvant treatment (up to Study Week 20)
Secondary outcome [3] 0 0
Global Health Status/Quality of Life (GHS/QoL) Score using the European Organization for Research and Treatment (EORTC) QoL Questionnaire (QLQ-C30)
Timepoint [3] 0 0
Baseline (cycle 1 in neoadjuvant phase) and end of follow-up (up to approximately 5 years)
Secondary outcome [4] 0 0
Adverse Events (AEs)
Timepoint [4] 0 0
Up to approximately 71 weeks
Secondary outcome [5] 0 0
Perioperative Complications
Timepoint [5] 0 0
Up to approximately 51 weeks following surgery
Secondary outcome [6] 0 0
Treatment Discontinuations Due to AEs
Timepoint [6] 0 0
Up to approximately 57 weeks

Eligibility
Key inclusion criteria
- Have previously untreated and pathologically confirmed resectable Stage II, IIIA, or
IIIB (N2) NSCLC.

- If male, must agree to use contraception or practice abstinence as well as refrain
from donating sperm during the treatment period and for the time needed to eliminate
each study intervention after the last dose of study intervention.

- If female, may participate if not pregnant or breastfeeding, and at least one of the
following conditions apply: 1) not a woman of childbearing potential (WOCBP); or 2) a
WOCBP who agrees to follow contraceptive guidance during the treatment period and for
the time needed to eliminate each study intervention after the last dose of study
intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store
for her own use for the purpose of reproduction during this period.

- Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for
submission. If blocks are not available, have unstained slides for submission for
central programmed death-ligand 1 (PD-L1) testing.

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within
10 days of randomization.

- Have 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 one of the following tumor locations/types:1) NSCLC involving the superior sulcus;
2) Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.

- Has a history of (non-infectious) pneumonitis /interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease that requires steroids.

- Has an active infection requiring systemic therapy.

- Has had an allogenic tissue/sold organ transplant.

- Has a known severe hypersensitivity (= Grade 3) to pembrolizumab, its active substance
and/or any of its excipients.

- Has a known severe hypersensitivity (= Grade 3) to any of the study chemotherapy
agents and/or to any of their excipients.

- Has an active autoimmune disease that has required systemic treatment in past 2 years.

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has a known history of Hepatitis B or Hepatitis C.

- Has a known history of active tuberculosis.

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the participant's
participation for the full duration of the trial, or is not in the best interest of
the participant to participate.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperating with the requirements of the trial.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another co-inhibitory T-cell receptor.

- Has received prior systemic anti-cancer therapy including investigational agents for
the current malignancy prior to randomization/allocation.

- Has received prior radiotherapy within 2 weeks of start of trial treatment.

- Has received a live vaccine within 30 days prior to the first dose of trial drug.

- Is currently participating in or has participated in a trial of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
trial treatment.

- Has a diagnosis of immunodeficiency or is receiving either systemic steroid therapy or
any other form of immunosuppressive therapy within 7 days prior the first dose of
trial drug.

- Has a known additional malignancy that is progressing or requires active treatment
within the past 5 years.

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 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
24/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/06/2026
Actual
Sample size
Target
Accrual to date
Final
797
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Orange Health Services ( Site 0624) - Orange
Recruitment hospital [2] 0 0
Westmead Hospital ( Site 0621) - Westmead
Recruitment postcode(s) [1] 0 0
2800 - Orange
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment outside Australia
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United States of America
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Arizona
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California
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Connecticut
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Delaware
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Santa Fe
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Cordoba
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San Juan
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Belgium
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Antwerpen
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Belgium
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Liege
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Belgium
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Vlaams-Brabant
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Ceara
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Hessen
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Oita
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Hiroshima
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Tokyo
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
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Seoul
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Vilnius
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Malaysia
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Sarawak
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Malaysia
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Kuala Lumpur
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Poland
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Dolnoslaskie
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Kujawsko-pomorskie
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Lodzkie
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Pomorskie
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Wielkopolskie
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Romania
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Bihor
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Romania
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Bucuresti
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Romania
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Cluj
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Romania
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Dolj
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Romania
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Ilfov
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Romania
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Timis
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Romania
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Brasov
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Romania
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Constanta
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Romania
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Suceava
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Russian Federation
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Chelyabinskaya Oblast
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Russian Federation
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Moskva
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Russian Federation
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Sankt-Peterburg
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Russian Federation
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Tatarstan, Respublika
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Russian Federation
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Tomskaya Oblast
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South Africa
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Gauteng
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South Africa
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Kwazulu-Natal
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South Africa
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Western Cape
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Spain
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Barcelona
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Spain
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La Coruna
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Spain
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Las Palmas
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Spain
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Madrid
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Spain
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Sevilla
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Taiwan
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Kaohsiung
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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
State/province [129] 0 0
Taoyuan
Country [130] 0 0
Ukraine
State/province [130] 0 0
Cherkaska Oblast
Country [131] 0 0
Ukraine
State/province [131] 0 0
Dnipropetrovska Oblast
Country [132] 0 0
Ukraine
State/province [132] 0 0
Ivano-Frankivska Oblast
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Ukraine
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Khersonska Oblast
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Ukraine
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Kirovohradska Oblast
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Ukraine
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Kyivska Oblast
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Ukraine
State/province [136] 0 0
Odeska Oblast
Country [137] 0 0
Ukraine
State/province [137] 0 0
Zaporizka Oblast
Country [138] 0 0
United Kingdom
State/province [138] 0 0
Leicestershire
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Liverpool
Country [140] 0 0
United Kingdom
State/province [140] 0 0
London, City Of
Country [141] 0 0
United Kingdom
State/province [141] 0 0
Nottinghamshire
Country [142] 0 0
United Kingdom
State/province [142] 0 0
Birmingham
Country [143] 0 0
United Kingdom
State/province [143] 0 0
Newcastle upon Tyne
Country [144] 0 0
United Kingdom
State/province [144] 0 0
Plymouth

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

Ethics approval
Ethics application status

Summary
Brief summary
This trial will evaluate the safety and efficacy of pembrolizumab (MK-3475) in combination
with platinum doublet neoadjuvant chemotherapy (NAC) before surgery [neoadjuvant phase],
followed by pembrolizumab alone after surgery [adjuvant phase] in participants with
resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer (NSCLC).
The primary hypotheses of this study are that neoadjuvant pembrolizumab (vs. placebo) in
combination with NAC, followed by surgery and adjuvant pembrolizumab (vs. placebo) will
improve: 1) event free survival (EFS) by biopsy assessed by local pathologist or by
investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors Version 1.1
(RECIST 1.1); and 2) overall survival (OS).
Trial website
https://clinicaltrials.gov/ct2/show/NCT03425643
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/NCT03425643