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

Sponsor
Alliance Foundation Trials, LLC. (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02591615
Collaborator
Merck Sharp & Dohme LLC (Industry)
90
Enrollment
15
Locations
2
Arms
69
Anticipated Duration (Months)
6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
90 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 1, 2016
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A

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

Drug: Carboplatin
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Names:
  • Paraplat
  • Paraplatin

    • Drug: Paclitaxel
    Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
    Other Names:
  • Taxol

    • Drug: Pemetrexed
    Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
    Other Names:
  • Alimta

    		•
    Active Comparator: Arm B

    MK-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

    Drug: MK-3475
    Dose frequency of Q3W, Day 1 of each cycle
    Other Names:
  • Pembrolizumab

    • Drug: Carboplatin
    Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
    Other Names:
  • Paraplat
  • Paraplatin

    • Drug: Paclitaxel
    Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
    Other Names:
  • Taxol

    • Drug: Pemetrexed
    Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
    Other Names:
  • Alimta

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) per RECIST 1.1 [18 Months]

      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

    1. Compare Progression-Free Survival (PFS) per RECIST 1.1 [24 Months]

      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.

    2. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [24 Months]

      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.

    Other Outcome Measures

    1. Evaluate the ORR per irRC [24 Months]

      To evaluate the ORR per irRC of MK-3475 administered prior to or after treatment with first-line carboplatin-based chemotherapy in patients with previously untreated NSCLC.

    2. Evaluate PFS per irRC [24 Months]

      To evaluate the PFS per irRC of previously untreated patients with advanced NSCLC who are treated with MK-3475 administered prior to or after first-line carboplatin-based chemotherapy.

    3. Evaluate Response Duration of MK-3475 [24 Months]

      To evaluate the response duration of MK-3475 based on schedule of administration with standard platinum-based chemotherapy in patients with previously untreated advanced NSCLC.

    4. Evaluate the Overall Survival (OS) [24 Months]

      To evaluate the overall survival (OS) of patients with previously untreated advanced NSCLC who received MK-3475 administered prior to or after treatment with first line carboplatin-based chemotherapy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSD Moores Cancer Center La Jolla California United States 92093
    2 The University of Chicago Medical Center Chicago Illinois United States 60637
    3 NorthShore University HealthSystem Evanston Illinois United States 60201
    4 Medical Oncology & Hematology Associates Des Moines Iowa United States 50309
    5 EMMC Cancer Care Brewer Maine United States 04412
    6 Metro MN Community Oncology Research Consortium Minneapolis Minnesota United States 55416
    7 University of Missouri - Ellis Fischel Cancer Center Columbia Missouri United States 65212
    8 Missouri Baptist Medical Center Saint Louis Missouri United States 63131
    9 NH Oncology (Concord) Concord New Hampshire United States 03301
    10 NH Oncology Hooksett New Hampshire United States 03106
    11 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    12 SUNY Upstate Medical University Syracuse New York United States 13210
    13 Wake Forest Baptist Health Winston-Salem North Carolina United States 27157
    14 The Ohio State University Columbus Ohio United States 43210
    15 University of Oklahoma Health Sciences Center Stephenson Cancer Center Oklahoma City Oklahoma United States 73104

    Sponsors and Collaborators

    • Alliance Foundation Trials, LLC.
    • Merck Sharp & Dohme LLC

    Investigators

    • Principal Investigator: Monica Bertagnolli, MD, Alliance Foundation Trials, LLC.
    • Study Chair: Thomas Hensing, MD, NorthShore University HealthSystem

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Alliance Foundation Trials, LLC.
    ClinicalTrials.gov Identifier:
    NCT02591615
    Other Study ID Numbers:
    • AFT-09
    First Posted:
    Oct 29, 2015
    Last Update Posted:
    Oct 4, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Paclitaxel
    Carboplatin
    Pembrolizumab
    Pemetrexed

    Study Results

    No Results Posted as of Oct 4, 2021