Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC
NCT ID: NCT02591615
Last Updated: 2022-12-28
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE2
Total Enrollment
91 participants
Study Classification
INTERVENTIONAL
Study Start Date
2016-03-31
Study Completion Date
2020-07-04
Brief Summary
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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
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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.
Conditions
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Non-Small Cell Lung Cancer
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
CROSSOVER
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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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
Group Type
ACTIVE_COMPARATOR
Carboplatin
Intervention Type
DRUG
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Paclitaxel
Intervention Type
DRUG
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Pemetrexed
Intervention Type
DRUG
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
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
Group Type
ACTIVE_COMPARATOR
MK-3475
Intervention Type
DRUG
Dose frequency of Q3W, Day 1 of each cycle
Carboplatin
Intervention Type
DRUG
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Paclitaxel
Intervention Type
DRUG
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Pemetrexed
Intervention Type
DRUG
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Interventions
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MK-3475
Dose frequency of Q3W, Day 1 of each cycle
Intervention Type
DRUG
Carboplatin
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Intervention Type
DRUG
Paclitaxel
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Intervention Type
DRUG
Pemetrexed
Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Intervention Type
DRUG
Other Intervention Names
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Pembrolizumab
Paraplat
Paraplatin
Taxol
Alimta
Eligibility Criteria
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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)
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.
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.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Sponsor Role
collaborator
Alliance Foundation Trials, LLC.
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Monica Bertagnolli, MD
Role: PRINCIPAL_INVESTIGATOR
Alliance Foundation Trials, LLC.
Thomas Hensing, MD
Role: STUDY_CHAIR
Endeavor Health
Locations
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UCSD Moores Cancer Center
La Jolla, California, United States
Site Status
The University of Chicago Medical Center
Chicago, Illinois, United States
Site Status
NorthShore University HealthSystem
Evanston, Illinois, United States
Site Status
Medical Oncology & Hematology Associates
Des Moines, Iowa, United States
Site Status
EMMC Cancer Care
Brewer, Maine, United States
Site Status
Metro MN Community Oncology Research Consortium
Minneapolis, Minnesota, United States
Site Status
NH Oncology (Concord)
Concord, New Hampshire, United States
Site Status
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
Site Status
SUNY Upstate Medical University
Syracuse, New York, United States
Site Status
The Ohio State University
Columbus, Ohio, United States
Site Status
University of Oklahoma Health Sciences Center Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Site Status
Countries
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United States
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Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
AFT-09
Identifier Type: -
Identifier Source: org_study_id