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

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.

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.
• Patients with sensitizing EGFR mutation or ALK rearrangement must have progressed on an appropriate tyrosine kinase inhibitor (TKI)

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.