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

November 28, 2022 updated by: Alliance Foundation Trials, LLC.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

91

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • UCSD Moores Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center
      • Evanston, Illinois, United States, 60201
        • Northshore University Healthsystem
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Medical Oncology & Hematology Associates
    • Maine
      • Brewer, Maine, United States, 04412
        • EMMC Cancer Care
    • Minnesota
      • Minneapolis, Minnesota, United States, 55416
        • Metro MN Community Oncology Research Consortium
    • New Hampshire
      • Concord, New Hampshire, United States, 03301
        • NH Oncology (Concord)
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New York
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center Stephenson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Paraplatin
  • Paraplat
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: Carboplatin
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Names:
  • Paraplatin
  • Paraplat
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
Drug: MK-3475
Dose frequency of Q3W, Day 1 of each cycle
Other Names:
  • Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) Per RECIST 1.1
Time Frame: 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). Overall Response (OR) = CR + PR.
18 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare Progression-Free Survival (PFS) Per RECIST 1.1
Time Frame: 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.
24 Months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time Frame: 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. A count of participants experiencing an adverse event is summarized here, the detailed summary is in the adverse events section of this report.
24 Months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the ORR Per irRC
Time Frame: 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.
24 Months
Evaluate PFS Per irRC
Time Frame: 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.
24 Months
Evaluate Response Duration of MK-3475
Time Frame: 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.
24 Months
Evaluate the Overall Survival (OS)
Time Frame: 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.
24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance Foundation Trials, LLC.

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Chair: Thomas Hensing, MD, Northshore University Healthsystem

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

January 4, 2019

Study Completion (Actual)

July 4, 2020

Study Registration Dates

First Submitted

October 20, 2015

First Submitted That Met QC Criteria

October 28, 2015

First Posted (Estimate)

October 29, 2015

Study Record Updates

Last Update Posted (Estimate)

December 28, 2022

Last Update Submitted That Met QC Criteria

November 28, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFT-09

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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