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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)

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ClinicalTrials.gov Identifier: NCT03631784
Recruitment Status : Recruiting
First Posted : August 15, 2018
Last Update Posted : December 10, 2018
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

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 : January 12, 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.



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

Locations
United States, California
St Joseph Heritage Healthcare ( Site 1403) Recruiting
Santa Rosa, California, United States, 95403
Contact: Study Coordinator    707-521-3830      
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      
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      
Australia, Victoria
Ballarat Health Services ( Site 0206) Recruiting
Ballarat, Victoria, Australia, 3350
Contact: Study Coordinator    +61353204735      
Korea, Republic of
Chungbuk National University Hospital ( Site 1003) Recruiting
Cheongju si, Chungcheongbuk Do, Korea, Republic of, 28644
Contact: Study Coordinator    +82432696015      
Samsung Medical Center ( Site 1001) Recruiting
Seoul, Korea, Republic of, 06351
Contact: Study Coordinator    +82234103459      
Ulsan University Hospital ( Site 1000) Recruiting
Ulsan, Korea, Republic of, 44033
Contact: Study Coordinator    +82522508832      
Poland
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0811) Recruiting
Bydgoszcz, Poland, 85-796
Contact: Study Coordinator    +48523743029      
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
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      
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      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

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: December 10, 2018
Last Verified: December 2018
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

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:
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
Pembrolizumab
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors