A Trial of Pembrolizumab in Combination With Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799, MK-3475-799)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab 200 mg; Paclitaxel 45 mg/m^2; Carboplatin AUC6; Cisplatin 75 mg/m^2; Pemetrexed 500 mg/m^2; Thoracic Radiation Therapy (TRT); Paclitaxel 200 mg/m^2; Carboplatin AUC2
Intervention description: Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles; 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.; Carboplatin AUC6 IV infusion on Day 1 of the 21-day cycle for Cycle 1.; Cisplatin 75 mg/m^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, 3.; Pemetrexed 500 mg/m^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, and 3.; The target total dose of TRT will be 60 Gy in 30 daily fractions of 2 Gy, prescribed to the planning target volume.; Paclitaxel 200 mg/m^2 IV infusion on Day 1 of the 21-day cycle of Cycle 1.; Carboplatin AUC2 IV infusion on Day 1, 8, 15 for Cycles 2 and 3 during radiation therapy.
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Pembrolizumab; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 217.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

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% and objective response rate (ORR) by blinded independent central review (BICR).
    

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.