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

• Sponsor: Alliance Foundation Trials, LLC.
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Alliance Foundation Trials, LLC.

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
Non-Small Cell Lung Cancer	Drug: MK-3475; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed	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

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Study Type :	Interventional (Clinical Trial)
Estimated 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 :	March 2016
Estimated Primary Completion Date :	April 2019
Estimated Study Completion Date :	December 2019

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 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: Paraplat; Paraplatin; 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

Outcome Measures

Primary Outcome Measures :

1. 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).

Secondary Outcome Measures :

1. 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.
2. 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.

Other Outcome Measures:

1. 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.
2. 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.
3. 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.
4. 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Contacts

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Contact: Ed Habermehl		info@alliancefoundationtrials.org

Locations

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United States, California
UCSD Moores Cancer Center	Recruiting
La Jolla, California, United States, 92093
Contact: Lyudmila Bazhenova, MD
Principal Investigator: Lyudmila Bazhenova
United States, Illinois
The University of Chicago Medical Center	Recruiting
Chicago, Illinois, United States, 60637
Contact: Jyoti Patel, MD
Principal Investigator: Jyoti Patel
NorthShore University HealthSystem	Recruiting
Evanston, Illinois, United States, 60201
Contact: Thomas Hensing, MD
Principal Investigator: Thomas Hensing
United States, Iowa
Medical Oncology & Hematology Associates	Recruiting
Des Moines, Iowa, United States, 50309
Contact: Robert Behrens, MD
Principal Investigator: Robert Behrens
United States, Maine
EMMC Cancer Care	Recruiting
Brewer, Maine, United States, 04412
Contact: Antoine Harb, MD
Principal Investigator: Antoine Harb
United States, Maryland
University of Maryland, Greenebaum Cancer Center	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Katherine Scilla, MD
Principal Investigator: Katherine Scilla
United States, Minnesota
Metro MN Community Oncology Research Consortium	Recruiting
Minneapolis, Minnesota, United States, 55416
Contact: Arkadiusz Dudek, MD
Principal Investigator: Arkadiusz Dudek
United States, Missouri
University of Missouri - Ellis Fischel Cancer Center	Recruiting
Columbia, Missouri, United States, 65212
Contact: Puja Nistala, MD
Principal Investigator: Puja Nistala
Missouri Baptist Medical Center	Recruiting
Saint Louis, Missouri, United States, 63131
Contact: Bryan Faller, MD
Principal Investigator: Bryan Faller
United States, Nebraska
Nebraska Methodist Hospital	Recruiting
Omaha, Nebraska, United States, 68114
Contact: Robert Langdon, MD
Principal Investigator: Robert Langdon
United States, New Hampshire
NH Oncology (Concord)	Recruiting
Concord, New Hampshire, United States, 03301
Contact: Douglas Weckstein, MD
Principal Investigator: Douglas Weckstein
NH Oncology	Recruiting
Hooksett, New Hampshire, United States, 03106
Contact: Douglas Weckstein, MD
Principal Investigator: Douglas Weckstein
Dartmouth Hitchcock Medical Center	Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Konstantin Dragnev, MD
Principal Investigator: Konstantin Dragnev
United States, New York
Hematology Oncology Associates of Central New York, PC	Recruiting
East Syracuse, New York, United States, 13057
Contact: Jeffrey Kirshner, MD
Principal Investigator: Jeffrey Kirshner
SUNY Upstate Medical University	Recruiting
Syracuse, New York, United States, 13210
Contact: Stephen Graziano, MD
Principal Investigator: Stephen Graziano
United States, North Carolina
Wake Forest Baptist Health	Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: William Petty, MD
Principal Investigator: William Petty
United States, Ohio
The Ohio State University	Recruiting
Columbus, Ohio, United States, 43210
Contact: Gregory Otterson, MD
Principal Investigator: Gregory Otterson
United States, Oklahoma
University of Oklahoma Health Sciences Center Stephenson Cancer Center	Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Raid Aljumaily, MD
Principal Investigator: Raid Aljumaily
United States, South Carolina
Lexington Oncology/ Lexington Medical Center	Recruiting
West Columbia, South Carolina, United States, 29169
Contact: James Wells, MD
Principal Investigator: James Wells

Sponsors and Collaborators

Alliance Foundation Trials, LLC.

Merck Sharp & Dohme Corp.

Investigators

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Principal Investigator:	Monica Bertagnolli, MD	Alliance Foundation Trials, LLC.

More Information

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Responsible Party:	Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier:	NCT02591615 History of Changes
Other Study ID Numbers:	AFT-09
First Posted:	October 29, 2015
Last Update Posted:	April 13, 2018
Last Verified:	April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:

Layout table for MeSH terms

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; Albumin-Bound 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