Purpose

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 IIB or IIIA 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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Have previously untreated, histologically confirmed NSCLC and histologically confirmed Stage IIB or IIIA NSCLC.
  • Be able to undergo protocol therapy, including necessary surgery.
  • 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NAC + Neoadjuvant/Adjuvant Pembrolizumab
Neoadjuvant: Prior to surgery, participants receive 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].
  • Biological: Pembrolizumab
    200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.
    Other names:
    • KEYTRUDA®
    • MK-3475
  • Drug: Cisplatin
    75 mg/m^2 by IV infusion Q3W, given on cycle day 1.
    Other names:
    • 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 names:
    • GEMZAR®
  • Drug: Pemetrexed
    500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.
    Other names:
    • Alimta®
Placebo Comparator
NAC + Neoadjuvant/Adjuvant Placebo
Neoadjuvant: Prior to surgery, participants receive 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].
  • 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 names:
    • 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 names:
    • GEMZAR®
  • Drug: Pemetrexed
    500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.
    Other names:
    • Alimta®

Recruiting Locations

Montefiore Medical Center ( Site 0016)
Bronx, New York 10461
Contact:
Study Coordinator
718-405-8027

More Details

NCT ID
NCT03425643
Status
Recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@merck.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.