Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: MK-3475; Carboplatin; Paclitaxel; Pemetrexed
Intervention description: Dose frequency of Q3W, Day 1 of each cycle; Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy); Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy); Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Intervention MeSH terms: Paclitaxel; Carboplatin; Pembrolizumab; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 91.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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:

          1. Be ≥ 18 years of age on day of signing informed consent.

          2. Have a life expectancy of at least 3 months.

          3. Have a histologically or cytologically confirmed diagnosis of stage IV NSCLC.

          4. Have a performance status of 0 or 1 on the ECOG.

          5. Have a measurable disease based on RECIST 1.1.

          6. Have provided tissue from an archival tissue sample or newly obtained core or
             excisional biopsy of tumor lesion.

          7. 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.

          8. Demonstrate adequate organ function.

          9. Female patient of childbearing potential should have a negative urine or serum
             pregnancy test within 72 hours.

         10. Female parents of childbearing potential must be willing to use 2 methods of birth
             control or be surgically sterile.

         11. Male patients must agree to use an adequate method of contraception.

         12. Patients with sensitizing EGFR mutation or ALK rearrangement must have progressed on
             an appropriate tyrosine kinase inhibitor (TKI)

        Exclusion Criteria:

          1. Has received prior treatment with chemotherapy or biologic therapy for stage IV NSCLC.

          2. Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device.

          3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy.

          4. 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.

          5. Has had prior chemotherapy or radiation.

          6. Has a known additional malignancy that is progressing or requires active treatment.

          7. Has known active CNS metastases and/or carcinomatous meningitis.

          8. 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.

          9. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

         10. Has an active infection requiring systemic therapy.

         11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial.

         12. Has known psychiatric or substance abuse disorders.

         13. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial.

         14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             CTLA-4 antibody.

         15. Has a known history of HIV.

         16. Has known active Hepatitis B or Hepatitis C.

         17. Has received a live vaccine within 30 days prior to the planned first dose of study
             therapy.

         18. Has a known history of active TB.

         19. Hypersensitivity to pembrolizumab or any of it's excipients.