Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC
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ClinicalTrials.gov Identifier: NCT02591615 |
Recruitment Status :
Completed
First Posted : October 29, 2015
Results First Posted : December 28, 2022
Last Update Posted : December 28, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Non-Small Cell Lung Cancer | Drug: MK-3475 Drug: Carboplatin Drug: Paclitaxel Drug: Pemetrexed | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 91 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 : | March 2016 |
Actual Primary Completion Date : | January 4, 2019 |
Actual Study Completion Date : | July 4, 2020 |

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:
Drug: Paclitaxel Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: Taxol Drug: Pemetrexed Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: 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 Name: Pembrolizumab Drug: Carboplatin Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Names:
Drug: Paclitaxel Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: Taxol Drug: Pemetrexed Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Other Name: Alimta |
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Be ≥ 18 years of age on day of signing informed consent.
- Have a life expectancy of at least 3 months.
- Have a histologically or cytologically confirmed diagnosis of stage IV NSCLC.
- Have a performance status of 0 or 1 on the ECOG.
- Have a measurable disease based on RECIST 1.1.
- Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of tumor lesion.
- 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.
- Demonstrate adequate organ function.
- Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours.
- Female parents of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile.
- Male patients must agree to use an adequate method of contraception.
- Patients with sensitizing EGFR mutation or ALK rearrangement must have progressed on an appropriate tyrosine kinase inhibitor (TKI)
Exclusion Criteria:
- Has received prior treatment with chemotherapy or biologic therapy for stage IV NSCLC.
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy.
- 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.
- Has had prior chemotherapy or radiation.
- Has a known additional malignancy that is progressing or requires active treatment.
- Has known active CNS metastases and/or carcinomatous meningitis.
- 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.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial.
- Has known psychiatric or substance abuse disorders.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody.
- Has a known history of HIV.
- Has known active Hepatitis B or Hepatitis C.
- Has received a live vaccine within 30 days prior to the planned first dose of study therapy.
- Has a known history of active TB.
- Hypersensitivity to pembrolizumab or any of it's excipients.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02591615
United States, California | |
UCSD Moores Cancer Center | |
La Jolla, California, United States, 92093 | |
United States, Illinois | |
The University of Chicago Medical Center | |
Chicago, Illinois, United States, 60637 | |
NorthShore University HealthSystem | |
Evanston, Illinois, United States, 60201 | |
United States, Iowa | |
Medical Oncology & Hematology Associates | |
Des Moines, Iowa, United States, 50309 | |
United States, Maine | |
EMMC Cancer Care | |
Brewer, Maine, United States, 04412 | |
United States, Minnesota | |
Metro MN Community Oncology Research Consortium | |
Minneapolis, Minnesota, United States, 55416 | |
United States, New Hampshire | |
NH Oncology (Concord) | |
Concord, New Hampshire, United States, 03301 | |
Dartmouth Hitchcock Medical Center | |
Lebanon, New Hampshire, United States, 03756 | |
United States, New York | |
SUNY Upstate Medical University | |
Syracuse, New York, United States, 13210 | |
United States, Ohio | |
The Ohio State University | |
Columbus, Ohio, United States, 43210 | |
United States, Oklahoma | |
University of Oklahoma Health Sciences Center Stephenson Cancer Center | |
Oklahoma City, Oklahoma, United States, 73104 |
Principal Investigator: | Monica Bertagnolli, MD | Alliance Foundation Trials, LLC. | |
Study Chair: | Thomas Hensing, MD | NorthShore University HealthSystem |
Documents provided by Alliance Foundation Trials, LLC.:
Responsible Party: | Alliance Foundation Trials, LLC. |
ClinicalTrials.gov Identifier: | NCT02591615 |
Other Study ID Numbers: |
AFT-09 |
First Posted: | October 29, 2015 Key Record Dates |
Results First Posted: | December 28, 2022 |
Last Update Posted: | December 28, 2022 |
Last Verified: | November 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Paclitaxel Carboplatin |
Pembrolizumab Pemetrexed Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Enzyme Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |