Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC

Status: Closed to Accrual


This is a multicenter randomized phase II to determine if the administration of standard platinum-based chemotherapy before MK-3475 in with Chemotherapy naive stage IV Non-small Cell Lung Cancer (NSCLC) will improve the overall response rate (ORR) compared to MK-3475 administered before chemotherapy. Patients will be given Pembrolizumab as maintenance up to 2 years: Carboplatin and paclitaxel or pemetrexed every 3 weeks x 4 cycles followed by pembrolizumab every 3 weeks for up to 2 years. Pembrolizumab every 3 weeks x 4 cycles followed by carboplatin and paclitaxel or pemetrexed every 3 weeks x 4 cycles followed by pembrolizumab every 3 weeks for up to 2 years.

Eligibility Criteria

Inclusion Criteria

  • Be ≥ 18 years of age on day of signing informed consent.
  • Have a life expectancy of at least 3 months.
  • Have a histologically or cytologically confirmed diagnosis of stage IV NSCLC.
  • Have a performance status of 0 or 1 on the ECOG.
  • Have a measurable disease based on RECIST 1.1.
  • Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of tumor lesion.
  • In patients with non-squamous non-small cell lung cancer, investigators must be able to produce source documentation of the EGFR mutation status or ALK translocation status.
  • Demonstrate adequate organ function.
  • Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours.
  • Female parents of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile.
  • Male patients must agree to use an adequate method of contraception.

Exclusion Criteria

  • Has received prior treatment with chemotherapy or biologic therapy for stage IV NSCLC.
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy.
  • Has had a prior mAb within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy or radiation.
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Has known active CNS metastases and/or carcinomatous meningitis.
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial.
  • Has known psychiatric or substance abuse disorders.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody.
  • Has a known history of HIV.
  • Has known active Hepatitis B or Hepatitis C.
  • Has received a live vaccine within 30 days prior to the planned first dose of study therapy.
  • Has a known history of active TB.
  • Hypersensitivity to pembrolizumab or any of it's excipients.

Locations & Contacts


University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Monica Marie Bertagnolli
Phone: 617-525-6457
Email: mbertagnolli@partners.org


University of Maryland / Greenebaum Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

While a genotype-directed strategy has been established as effective in treatment selection for patients with advanced NSCLC, only a minority of patients at this time will have a readily identifiable actionable molecular target. Furthermore, genotype-directed therapy has not been validated for patients with squamous cell carcinoma of the lung. Therefore, the majority of patients with advanced NSCLC will continue to rely on standard platinum-based doublet chemotherapy. Given the plateau in effectiveness of this approach, novel treatment strategies are clearly warranted.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
Alliance Foundation Trials, LLC.

Trial IDs

Primary ID AFT-09
Secondary IDs NCI-2016-00099
Clinicaltrials.gov ID NCT02591615