Clinical Trials /

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

NCT03631784

Description:

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%.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 3475-799
  • SECONDARY ID: MK-3475-799
  • NCT ID: NCT03631784

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
Pembrolizumab 200 mgMK-3475Cohort A
Paclitaxel 45 mg/m^2Cohort A
Carboplatin AUC6Cohort A
Cisplatin 75 mg/m^2Cohort B
Pemetrexed 500 mg/m^2Cohort B
Paclitaxel 200 mg/m^2Cohort A
Carboplatin AUC2Cohort A

Purpose

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%.

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalParticipants 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.
  • Pembrolizumab 200 mg
  • Paclitaxel 45 mg/m^2
  • Carboplatin AUC6
  • Paclitaxel 200 mg/m^2
  • Carboplatin AUC2
Cohort BExperimentalParticipants 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.
  • Pembrolizumab 200 mg
  • Cisplatin 75 mg/m^2
  • Pemetrexed 500 mg/m^2

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Who Develop Grade 3 or Higher Pneumonitis
Time Frame:Up to approximately 1 year
Safety Issue:
Description:Pneumonitis is an immune-mediated adverse event which is of interest in light of the mechanism of action of pembrolizumab.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Up to approximately 1 year
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 1 year
Safety Issue:
Description:OS is defined as the time from enrollment to death due to any cause.
Measure:Adverse Events (AEs)
Time Frame:Up to approximately 1 1/4 years
Safety Issue:
Description:Percentage of participants who experienced one or more AEs.
Measure:Discontinuations due to AEs
Time Frame:Up to approximately 1 year
Safety Issue:
Description:Percentage of participants discontinuing study treatment(s) due to an AE.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • PD1
  • PD-1
  • PDL1
  • PD-L1

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