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History of Changes for Study: NCT03631784
A Trial of Pembrolizumab in Combination With Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799, MK-3475-799). (KEYNOTE-799)
Latest version (submitted November 1, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 13, 2018 None (earliest Version on record)
2 August 20, 2018 Study Status
3 September 14, 2018 Recruitment Status, Study Status and Contacts/Locations
4 September 24, 2018 Study Status
5 October 24, 2018 Arms and Interventions, Study Status, Contacts/Locations, Eligibility, Outcome Measures and Oversight
6 November 9, 2018 Contacts/Locations and Study Status
7 November 15, 2018 Contacts/Locations and Study Status
8 November 22, 2018 Contacts/Locations and Study Status
9 November 29, 2018 Contacts/Locations and Study Status
10 December 6, 2018 Study Status, IPDSharing and Contacts/Locations
11 December 13, 2018 Contacts/Locations and Study Status
12 December 19, 2018 Study Status and Contacts/Locations
13 December 27, 2018 Contacts/Locations and Study Status
14 January 10, 2019 Study Status and Contacts/Locations
15 January 18, 2019 Contacts/Locations and Study Status
16 January 31, 2019 Contacts/Locations and Study Status
17 February 8, 2019 Study Status and Contacts/Locations
18 March 1, 2019 Contacts/Locations and Study Status
19 March 8, 2019 Study Status and Contacts/Locations
20 March 14, 2019 Contacts/Locations and Study Status
21 March 22, 2019 Contacts/Locations and Study Status
22 March 26, 2019 Contacts/Locations and Study Status
23 April 5, 2019 Study Status and Contacts/Locations
24 April 11, 2019 Contacts/Locations and Study Status
25 April 17, 2019 Contacts/Locations and Study Status
26 April 26, 2019 Contacts/Locations and Study Status
27 May 3, 2019 Contacts/Locations and Study Status
28 May 22, 2019 Contacts/Locations and Study Status
29 June 19, 2019 Study Status and Contacts/Locations
30 July 18, 2019 Study Status and Contacts/Locations
31 August 8, 2019 Study Status and Contacts/Locations
32 October 10, 2019 Contacts/Locations and Study Status
33 January 17, 2020 Study Status, References and Contacts/Locations
34 January 27, 2020 Contacts/Locations and Study Status
35 March 27, 2020 Contacts/Locations and Study Status
36 April 17, 2020 Contacts/Locations and Study Status
37 April 23, 2020 Contacts/Locations and Study Status
38 April 29, 2020 Contacts/Locations and Study Status
39 May 7, 2020 Study Status and Contacts/Locations
40 May 15, 2020 Contacts/Locations and Study Status
41 May 28, 2020 Contacts/Locations and Study Status
42 June 9, 2020 Contacts/Locations and Study Status
43 July 3, 2020 Study Status and Contacts/Locations
44 July 15, 2020 Recruitment Status, Study Status and Contacts/Locations
45 December 22, 2020 Study Status
46 September 6, 2021 Study Status
47 November 1, 2021 Study Status, Study Design and References
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Study NCT03631784
Submitted Date:  August 13, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: 3475-799
Brief Title: A Trial of Pembrolizumab in Combination With Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799, MK-3475-799). (KEYNOTE-799)
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).
Secondary IDs: MK-3475-799 [Merck Protocol Number]
Open or close this module Study Status
Record Verification: August 2018
Overall Status: Not yet recruiting
Study Start: September 17, 2018
Primary Completion: December 15, 2020 [Anticipated]
Study Completion: January 12, 2021 [Anticipated]
First Submitted: August 13, 2018
First Submitted that
Met QC Criteria:
August 13, 2018
First Posted: August 15, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
August 13, 2018
Last Update Posted: August 15, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
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%.
Detailed Description:
Open or close this module Conditions
Conditions: Non-small Cell Lung Cancer
Keywords: PD1
PD-1
PDL1
PD-L1
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 216 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort A
Participants will receive 1 cycle of carboplatin area under the curve (AUC)6 with paclitaxel 200 mg/m^2 and pembrolizumab 200 mg on Day 1. Approximately 3 weeks later, participants will receive carboplatin AUC2 with paclitaxel 45 mg/m^2 administered weekly for 6 weeks along with 2 cycles of pembrolizumab 200 mg administered every 3 weeks (Q3W) in conjunction with standard thoracic radiotherapy. 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 Names:
  • 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 1, 2, and 3
Drug: Carboplatin AUC6
Carboplatin AUC6 IV infusion on Day 1, 8, 15 of each 3-week cycle for Cycles 1, 2, and 3
Radiation: Thoracic Radiotherapy
Standard Fractionation of 2 Gray (Gy)/fraction at 60 Gy
Experimental: Cohort B
Participants will receive 3 cycles of cisplatin 75 mg/m^2 with pemetrexed 500 mg/m^2 and pembrolizumab 200 mg on Day 1 of each 3- week cycle. Treatment will be given in conjunction with standard thoracic radiotherapy 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 Names:
  • MK-3475
Drug: Cisplatin 75 mg/m^2
Cisplatin 75 mg/m^2 IV infusion on Day 1 of each 3-week cycle for Cycles 1, 2, 3
Drug: Pemetrexed 500 mg/m^2
Pemetrexed 500 mg/m^2 IV infusion on Day 1 of each 3-week cycle Cycles 1, 2, and 3
Radiation: Thoracic Radiotherapy
Standard Fractionation of 2 Gray (Gy)/fraction at 60 Gy
Open or close this module Outcome Measures
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 or death due to any cause, whichever occurs first assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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, 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 archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • 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.
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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