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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)

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ClinicalTrials.gov Identifier: NCT03425643
Recruitment Status : Recruiting
First Posted : February 7, 2018
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE February 2, 2018
First Posted Date  ICMJE February 7, 2018
Last Update Posted Date January 28, 2020
Actual Study Start Date  ICMJE April 24, 2018
Estimated Primary Completion Date January 20, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2018)
  • Event Free Survival (EFS) [ Time Frame: Up to 5 years ]
    EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by blinded central pathologist or by imaging using RECIST 1.1 assessed by BICR.
  • Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time from randomization until death from any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03425643 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2018)
  • Major Pathological Response (mPR) Rate [ Time Frame: Up to 7 weeks following completion of neoadjuvant treatment (up to Study Week 20) ]
    mPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy.
  • Pathological Complete Response (pCR) Rate [ Time Frame: Up to 7 weeks following completion of neoadjuvant treatment (up to Study Week 20) ]
    pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.
  • Global Health Status/Quality of Life (GHS/QoL) Score using the European Organization for Research and Treatment (EORTC) QoL Questionnaire (QLQ-C30) [ Time Frame: Baseline (cycle 1 in neoadjuvant phase) and end of follow-up (up to 5 years) ]
    Change from baseline in GHS/QoL score using the EORTC QLQ-C30 will be determined. The EORTC QLQ-C30 is the most widely used cancer-specific, health-related QoL instrument comprised of 30 individual items arranged as both multi-item scales and individual items. Specifically, these items are divided into 5 functional scales (15 items total), 3 symptom scales (7 items total), 6 individual items, and a GHS/QoL scale composed of 2 items: GHS and QoL. The GHS/QoL score measured here refers to only the composite score calculated for the GHS/QoL scale. Both items on the GHS/QoL scale are scored from 1 (very poor GHS/QoL) to 7 (excellent GHS/QoL) and scores for both items are averaged and a linear transformation applied to standardize the overall GHS/QoL score from 0 to 100, with higher overall scores indicating higher GHS/QoL.
  • Adverse Events (AEs) [ Time Frame: Up to 71 weeks ]
    The number of participants experiencing an AE will be assessed. An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
  • Perioperative Complications [ Time Frame: Up to 51 weeks following surgery ]
    The number of participants experiencing perioperative complications will be assessed. Perioperative complications are a discrete set of both intraoperative and postoperative complications, potentially contributing to increased length of inpatient care and/or delay of adjuvant therapy.
  • Treatment Discontinuations Due to AEs [ Time Frame: Up to 57 weeks ]
    The number of participants discontinuing study therapy due to an AE will be assessed.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
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 blinded central pathologist or by imaging using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by blinded independent central review (BICR); and 2) overall survival (OS).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Biological: Pembrolizumab
    200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.
    Other Names:
    • KEYTRUDA®
    • MK-3475
  • Drug: Placebo
    Normal saline by IV infusion Q3W, given on cycle day 1.
  • Drug: Cisplatin
    75 mg/m^2 by IV infusion Q3W, given on cycle day 1.
    Other Name: PLATINOL®
  • Drug: Gemcitabine
    1000 mg/m^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC.
    Other Name: GEMZAR®
  • Drug: Pemetrexed
    500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.
    Other Name: Alimta®
Study Arms  ICMJE
  • 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]. Participants who receive radiotherapy without undergoing surgery will not receive adjuvant therapy.

    Interventions:
    • Biological: Pembrolizumab
    • Drug: Cisplatin
    • Drug: Gemcitabine
    • Drug: Pemetrexed
  • 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]. Participants who receive radiotherapy without undergoing surgery will not receive adjuvant therapy.

    Interventions:
    • Drug: Placebo
    • Drug: Cisplatin
    • Drug: Gemcitabine
    • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 2, 2018)
786
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 29, 2026
Estimated Primary Completion Date January 20, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC.
  • Be able to undergo protocol therapy, including necessary surgery. A positron emission tomography (PET) scan may be utilized as a surrogate for pathologic staging of N1 lymph nodes for participants with T2b and T4 tumors.
  • If male, must agree to use contraception or practice abstinence as well as refrain from donating sperm for at least 180 days after the last dose of study treatment.
  • If female, may participate if not pregnant, not 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 at least 180 days after the last dose of study treatment.
  • 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.

Exclusion Criteria:

  • A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment.
  • 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.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Argentina,   Belgium,   Brazil,   Canada,   China,   France,   Germany,   Ireland,   Italy,   Japan,   Korea, Republic of,   Poland,   Romania,   Russian Federation,   South Africa,   Spain,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03425643
Other Study ID Numbers  ICMJE 3475-671
2017-001832-21 ( EudraCT Number )
MK-3475-671 ( Other Identifier: Merck Protocol Number )
183970 ( Other Identifier: JAPIC-CTI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP