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A Trial of Pembrolizumab in Combination With Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799, MK-3475-799). (KEYNOTE-799)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03631784
Recruitment Status : Recruiting
First Posted : August 15, 2018
Last Update Posted : October 11, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a trial in adult participants with unresectable, locally advanced, Stage III non-small cell lung cancer (NSCLC) treated with pembrolizumab in combination with platinum doublet chemotherapy and standard thoracic radiotherapy followed by pembrolizumab monotherapy. The primary hypothesis of the trial is that within each platinum doublet chemotherapy cohort, the percentage of participants who develop Grade 3 or higher pneumonitis is ≤10%.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Pembrolizumab 200 mg Drug: Paclitaxel 45 mg/m^2 Drug: Carboplatin AUC6 Drug: Cisplatin 75 mg/m^2 Drug: Pemetrexed 500 mg/m^2 Radiation: Thoracic Radiation Therapy (TRT) Drug: Paclitaxel 200 mg/m^2 Drug: Carboplatin AUC2 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 216 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of Pembrolizumab (MK-3475) in Combination With Platinum Doublet Chemotherapy and Radiotherapy for Participants With Unresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC) (KEYNOTE-799).
Actual Study Start Date : October 19, 2018
Estimated Primary Completion Date : December 15, 2020
Estimated Study Completion Date : March 14, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A
Participants will receive 1 cycle of pembrolizumab 200 mg on Day 1 with paclitaxel 200 mg/m^2, and carboplatin area under the curve (AUC) AUC6. Approximately 3 weeks later, participants will receive 2 cycles of pembrolizumab 200 mg administered every 3 weeks (Q3W) and carboplatin AUC2 with paclitaxel 45 mg/m^2 administered weekly for 6 weeks in conjunction with standard thoracic radiotherapy (60 Gray [Gy]). To conclude the study treatments, participants will receive 14 additional cycles of pembrolizumab 200 mg administered Q3W.
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles
Other Name: MK-3475

Drug: Paclitaxel 45 mg/m^2
Paclitaxel 45 mg/m^2 IV infusion on Days 1, 8, 15 of each 3-week cycle for Cycles 2, and 3 during radiation therapy.

Drug: Carboplatin AUC6
Carboplatin AUC6 IV infusion on Day 1 of the 21-day cycle for Cycle 1.

Radiation: Thoracic Radiation Therapy (TRT)
The target total dose of TRT will be 60 Gy in 30 daily fractions of 2 Gy, prescribed to the planning target volume.

Drug: Paclitaxel 200 mg/m^2
Paclitaxel 200 mg/m^2 IV infusion on Day 1 of the 21-day cycle of Cycle 1.

Drug: Carboplatin AUC2
Carboplatin AUC2 IV infusion on Day 1, 8, 15 for Cycles 2 and 3 during radiation therapy.

Experimental: Cohort B
Participants will receive 3 cycles of pembrolizumab 200 mg on Day 1 of each 3-week cycle and 3 cycles of pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2. Treatment will be given in conjunction with standard thoracic radiotherapy (60 Gy) in Cycles 2 and 3. To conclude the study treatments, participants will receive 14 additional cycles of pembrolizumab 200 mg administered Q3W.
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles
Other Name: MK-3475

Drug: Cisplatin 75 mg/m^2
Cisplatin 75 mg/m^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, 3.

Drug: Pemetrexed 500 mg/m^2
Pemetrexed 500 mg/m^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, and 3.

Radiation: Thoracic Radiation Therapy (TRT)
The target total dose of TRT will be 60 Gy in 30 daily fractions of 2 Gy, prescribed to the planning target volume.




Primary Outcome Measures :
  1. Percentage of Participants Who Develop Grade 3 or Higher Pneumonitis [ Time Frame: Up to approximately 1 year ]
    Pneumonitis is an immune-mediated adverse event which is of interest in light of the mechanism of action of pembrolizumab.

  2. Percentage of Participants with a Complete or Partial Response [ Time Frame: Up to approximately 1 year ]

    Complete Response (CR):

    Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Partial Response (PR):

    At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.



Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to approximately 1 year ]
    PFS defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause, whichever occurs first, as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

  2. Overall Survival (OS) [ Time Frame: Up to approximately 1 year ]
    OS is defined as the time from enrollment to death due to any cause.

  3. Adverse Events (AEs) [ Time Frame: Up to approximately 1 1/4 years ]
    Percentage of participants who experienced one or more AEs.

  4. Discontinuations due to AEs [ Time Frame: Up to approximately 1 year ]
    Percentage of participants discontinuing study treatment(s) due to an AE.



Information from the National Library of Medicine

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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:

  • Male/female participants, who are at least 18 years of age on the day of signing informed consent with previously untreated, unresectable, pathologically confirmed NSCLC and Stage IIIA, IIIB or IIIC NSCLC by American Joint Committee on Cancer Version 8.
  • No evidence of metastatic disease by whole body positron emission tomography/computed tomography (PET/ CT) scan, diagnostic quality CT scan, and brain imaging.
  • Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
  • Have provided tumor tissue sample (core, incisional, or excisional biopsy).
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Have adequate pulmonary function test (PFT)
  • Have adequate organ function
  • A male participant must agree to use contraception through the end of treatment and refrain from donating sperm during this period.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and if participant is a woman of childbearing potential (WOCBP), agrees to follow the contraceptive guidance as provided in the protocol through the end of treatment.

Exclusion Criteria:

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment allocation
  • Has small cell lung cancer.
  • Has had documented weight loss >10% in the preceding 3 months.
  • Participants whose radiation treatment plans are likely to encompass a volume of whole lung receiving >20 Gy in total (V20) of more than 31% of lung volume.
  • Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus or for breast cancer.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (programmed cell death protein 1 [PD-1] and its ligands, programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 [PD-L2]) or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
  • Has received a live vaccine within 30 days prior to the first dose of study drug.
  • Has had an allogenic tissue/solid organ transplant.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg prednisone daily or equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
  • Has severe hypersensitivity (Grade 3 or higher) to pembrolizumab and/or any of its excipients.
  • Has a known severe hypersensitivity (Grade 3 or higher) to any of the study chemotherapy agents and/or to any of their excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
  • Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has a known psychiatric or substance abuse disorder that would interfere with cooperating with the requirements of the study.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study through the end of treatment.

Information from the National Library of Medicine

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): NCT03631784


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

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Locations
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United States, California
St Joseph Heritage Healthcare ( Site 1403) Recruiting
Santa Rosa, California, United States, 95403
Contact: Study Coordinator    707-521-3830      
United States, Illinois
North Shore University Health System ( Site 1413) Recruiting
Evanston, Illinois, United States, 60201
Contact: Study Coordinator    847-570-2109      
United States, Indiana
Parkview Cancer Institute ( Site 1415) Recruiting
Fort Wayne, Indiana, United States, 46845
Contact: Study Coordinator    833-724-8356      
United States, Massachusetts
UMass Memorial Medical Center ( Site 1417) Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Study Coordinator    508-334-5539      
United States, Michigan
Henry Ford Hospital ( Site 1418) Recruiting
Detroit, Michigan, United States, 48202
Contact: Study Coordinator    313-916-2635      
United States, Nebraska
St. Francis Cancer Treatment Center ( Site 1421) Recruiting
Grand Island, Nebraska, United States, 68803
Contact: Study Coordinator    308-398-5450      
United States, New Jersey
Rutgers Cancer Institute of New Jersey ( Site 1422) Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Study Coordinator    732-235-6048      
United States, Oklahoma
CTCA Southwestern ( Site 1428) Recruiting
Tulsa, Oklahoma, United States, 74133
Contact: Study Coordinator    918-286-5448      
United States, Pennsylvania
Fox Chase Cancer Center ( Site 1433) Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Study Coordinator    215-728-5862      
United States, South Dakota
Sanford Cancer Center Oncology Clinic ( Site 1434) Recruiting
Sioux Falls, South Dakota, United States, 57104
Contact: Study Coordinator    605-328-8000      
Australia, New South Wales
Blacktown Hospital Western Sydney Local Health District ( Site 0204) Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Study Coordinator    +61403170371      
MNCCI Port Macquarie Base Hospital ( Site 0200) Recruiting
Port Macquarie, New South Wales, Australia, 2444
Contact: Study Coordinator    +61265801818      
Southern Medical Day Care Centre ( Site 0201) Active, not recruiting
Wollongong, New South Wales, Australia, 2500
Australia, Victoria
Ballarat Health Services ( Site 0206) Recruiting
Ballarat, Victoria, Australia, 3350
Contact: Study Coordinator    +61353204735      
France
Clinique de L'Europe ( Site 0308) Recruiting
Amiens, France, 80000
Contact: Study Coordinator    +33360125235      
ICO Centre Paul Papin ( Site 0309) Recruiting
Angers, France, 49100
Contact: Study Coordinator    +33241352775      
CHU Jean Minjoz ( Site 0301) Recruiting
Besancon, France, 25000
Contact: Study Coordinator    +33370632440      
Centre Jean Perrin ( Site 0304) Recruiting
Clermont Ferrand, France, 63011
Contact: Study Coordinator    +33473278141      
Clinique Clairval ( Site 0311) Recruiting
Marseille, France, 13009
Contact: Study Coordinator    +33609957536      
Institut du Cancer de Montpellier ( Site 0300) Recruiting
Montpellier, France, 34298
Contact: Study Coordinator    +33681329401      
C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0302) Recruiting
Rennes., France, 35033
Contact: Study Coordinator    +33299289795      
C.H. de Saint Quentin ( Site 0306) Recruiting
Saint Quentin, France, 02321
Contact: Study Coordinator    +33360125235      
Institut de Cancerologie Gustave Roussy ( Site 0305) Recruiting
Villejuif, France, 94800
Contact: Study Coordinator    +33142114211      
Germany
Charite Universitaetsmedizin Berlin - Campus-Virchow-Klinikum ( Site 0414) Recruiting
Berlin, Germany, 13353
Contact: Study Coordinator    +4930450665005      
Augusta-Kranken-Anstalt Bochum ( Site 0401) Recruiting
Bochum, Germany, 44791
Contact: Study Coordinator    +492345172430      
Klinikum Chemnitz gGmbH ( Site 0410) Recruiting
Chemnitz, Germany, 09113
Contact: Study Coordinator    +4937133343550      
LungenClinic Grosshansdorf GmbH ( Site 0408) Recruiting
Grosshansdorf, Germany, 22927
Contact: Study Coordinator    +494102601188      
Katholisches Marienkrankenhaus gGmbH ( Site 0411) Recruiting
Hamburg, Germany, 22087
Contact: Study Coordinator    +494025462508      
Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0404) Recruiting
Heidelberg, Germany, 69126
Contact: Study Coordinator    +4962213961304      
Universitatsklinikum Mannheim GmbH ( Site 0413) Recruiting
Mannheim, Germany, 68167
Contact: Study Coordinator    +496213832855      
Bethanien Krankenhaus Moers ( Site 0406) Recruiting
Moers, Germany, 47441
Contact: Study Coordinator    +4928412002828      
Korea, Republic of
Chungbuk National University Hospital ( Site 1003) Recruiting
Cheongju si, Chungcheongbuk Do, Korea, Republic of, 28644
Contact: Study Coordinator    +82432696015      
National Cancer Center ( Site 1002) Recruiting
Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
Contact: Study Coordinator    +82319201154      
Samsung Medical Center ( Site 1001) Recruiting
Seoul, Korea, Republic of, 06351
Contact: Study Coordinator    +82234103459      
Ulsan University Hospital ( Site 1000) Completed
Ulsan, Korea, Republic of, 44033
New Zealand
Auckland City Hospital ( Site 0700) Recruiting
Auckland, New Zealand, 1023
Contact: Study Coordinator    +6493074949      
Poland
Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0813) Recruiting
Koszalin, Zachodniopomorskie, Poland, 75-581
Contact: Study Coordinator    +48502204953      
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0811) Recruiting
Bydgoszcz, Poland, 85-796
Contact: Study Coordinator    +48523743029      
Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 0812) Recruiting
Gdynia, Poland, 81-519
Contact: Study Coordinator    +48602788669      
Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym ( Site 0802) Recruiting
Krakow, Poland, 31-826
Contact: Study Coordinator    +48721295010      
Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 0800) Recruiting
Warszawa, Poland, 02-781
Contact: Study Coordinator    +48225463066      
Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0910) Recruiting
Kazan, Russian Federation, 420029
Contact: Study Coordinator    +79172662851      
N.N. Blokhin National Medical Oncology Research Centre ( Site 0902) Recruiting
Moscow, Russian Federation, 115478
Contact: Study Coordinator    +79031990755      
National Medical Research Center of Oncology n.a. N. N. Petrov ( Site 0904) Recruiting
St. Petersburg, Russian Federation, 197758
Contact: Study Coordinator    +79117500005      
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0903) Recruiting
Ufa, Russian Federation, 450054
Contact: Study Coordinator    +79050058625      
Spain
Hospital Universitari Vall d Hebron ( Site 1101) Recruiting
Barcelona, Spain, 08035
Contact: Study Coordinator    +34934894158      
Hospital Clinic de Barcelona ( Site 1100) Recruiting
Barcelona, Spain, 08036
Contact: Study Coordinator    +34932275402      
Clinica Universitaria de Navarra ( Site 1102) Recruiting
Madrid, Spain, 28027
Contact: Study Coordinator    +349135319027502      
Hospital Son Llatzer ( Site 1105) Recruiting
Palma de Mallorca, Spain, 07198
Contact: Study Coordinator    +348712020001629      
Hospital Universitario Virgen Macarena ( Site 1103) Recruiting
Sevilla, Spain, 41009
Contact: Study Coordinator    +34955008932      
United Kingdom
Leeds Teaching Hospitals NHS Trust ( Site 1209) Recruiting
Leeds, United Kingdom, LS9 7TF
Contact: Study Coordinator    +441132068225      
Royal Free NHS Foundation Trust ( Site 1200) Recruiting
London, United Kingdom, NW3 2QG
Contact: Study Coordinator    +442033111742      
Charing Cross Hospital ( Site 1208) Recruiting
London, United Kingdom, W6 8RF
Contact: Study Coordinator    +442033130806      
Queen's Hospital ( Site 1201) Recruiting
Rom Valley, United Kingdom, RM7 0AG
Contact: Study Coordinator    +4417084350003440      
Southampton General Hospital ( Site 1204) Recruiting
Southampton, United Kingdom, SO16 6YD
Contact: Study Coordinator    +442381206184      
Beacon Centre ( Site 1203) Recruiting
Taunton, United Kingdom, TA1 5DA
Contact: Study Coordinator    +447941036266      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03631784     History of Changes
Other Study ID Numbers: 3475-799
MK-3475-799 ( Other Identifier: Merck Protocol Number )
First Posted: August 15, 2018    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1
Additional relevant MeSH terms:
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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
Cisplatin
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