Clinical Trials /

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

NCT02591615

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC
  • Official Title: Randomized Phase II Trial Evaluating the Optimal Sequencing of PD-1 Inhibition With Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in Patients With Chemotherapy Naive Stage IV Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: AFT-09
  • NCT ID: NCT02591615

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
MK-3475PembrolizumabArm B
CarboplatinParaplat, ParaplatinArm A
PaclitaxelTaxolArm A
PemetrexedAlimtaArm A

Purpose

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.

Detailed Description

      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 Arms

NameTypeDescriptionInterventions
Arm AActive ComparatorFor Squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles OR For Non-squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles
  • Carboplatin
  • Paclitaxel
  • Pemetrexed
Arm BActive ComparatorMK-3475 200 mg/m2 IV every 21-days for up to 4 cycles Patients with CR, PR, or SD by irRC will then be treated with: For Squamous Carcinoma: Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles OR For Non-squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles
  • MK-3475
  • Carboplatin
  • Paclitaxel
  • Pemetrexed

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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) per RECIST 1.1
Time Frame:18 Months
Safety Issue:
Description:The primary objective of this randomized phase II trial to determine the overall response rate (ORR per RECIST 1.1) in Chemotherapy naive patients with stage IV NSCLC after the administration of standard platinum-based chemotherapy before MK-3475 (arm A) and administration of MK-3475 administered before standard platinum-based chemotherapy (arm B).

Secondary Outcome Measures

Measure:Compare Progression-Free Survival (PFS) per RECIST 1.1
Time Frame:24 Months
Safety Issue:
Description:To compare the progression-free survival (PFS) per RECIST 1.1 in previously untreated patients with advanced NSCLC treated with first line carboplatin-based chemotherapy followed by MK-3475 to patients treated with MK-3475 prior to first-line carboplatin-based chemotherapy.
Measure:Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time Frame:24 Months
Safety Issue:
Description:To characterize the adverse events related to MK-3475 by frequency, type and grade in patients with Chemotherapy naive advanced NSCLC based on the sequence of administration with first-line chemotherapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Alliance Foundation Trials, LLC.

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