Consolidation Pembrolizumab Following Chemoradiation in Patients With Inoperable/Unresectable Stage III NSCLC

A Phase II Trial of Concurrent Chemoradiation With Consolidation Pembrolizumab for the Treatment of Inoperable or Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC): HCRN LUN14-179

This is an open label, multi-institutional, single arm phase II trial of consolidation therapy with pembrolizumab, following initial treatment with concurrent chemoradiation in patients with inoperable or unresectable stage IIIA or IIIB NSCLC. No randomization or blinding is involved.

OUTLINE: This is a multi-center study.

Eligible patients must have completed concurrent chemoradiation with a standard chemotherapy regimen (either cisplatin/etoposide or carboplatin/paclitaxel) and a dose of radiation ranging from 59.4-66.6Gy, with restaging completed 28 days to 56 days post-chemoradiation. Patients with progressive disease will not be eligible for investigational treatment. Patients with stable disease/response will be eligible to register for investigational treatment of consolidation therapy to begin a minimum of 28 days and a maximum of 56 days from completion of chemoradiotherapy.

INVESTIGATIONAL TREATMENT:

Pembrolizumab, 200 mg IV every 3 weeks (until progressive disease (PD), unacceptable toxicity, or after 12 months (52 weeks) of therapy with pembrolizumab.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Hematopoietic:

• Absolute neutrophil count (ANC) ≥1,500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L

Renal:

• Serum creatinine OR measured or calculated creatinine clearance ≤1.5 X institutional upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl)

Hepatic:

• Serum total bilirubin ≤ 1.5 X institutional ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 institutional ULN
• Aspartate transaminase (AST), serum glutamic oxaloacetic transaminase (SGOT), alanine transaminase (ALT), serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 X institutional ULN

Coagulation:

• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X institutional ULN unless subject is receiving anticoagulant therapy as long as PT/INR/PTT is within therapeutic range of intended use of anticoagulants.

Inclusion Criteria:

• Histological or cytological evidence of NSCLC
• Must have unresectable or inoperable stage IIIA or IIIB disease. Patients are considered unresectable or inoperable based on the judgment of the treating physician
• Must have completed concurrent chemoradiation with a standard chemotherapy regimen (either cisplatin/etoposide or carboplatin/paclitaxel) and a dose of radiation ranging from 59.4-66.6Gy
• Must have stable disease or disease response as evidenced on CT evaluation a minimum of 28 days and a maximum of 56 days following the completion of chemoradiation
• Women of childbearing potential must be willing to use two methods of contraception or abstain from heterosexual activity from the point of registration through 120 days after the last dose of study drug
• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of the study drug through 120 days after the last dose of the study drug
• Age ≥ 18 years at the time of consent
• Written informed consent and HIPAA authorization for release of personal health information

Exclusion Criteria:

• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Active central nervous system (CNS) metastases. Subjects must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration for protocol therapy to exclude brain metastases if symptomatic or without prior brain imaging
• Treatment with any investigational agent within 28 days prior to registration for protocol therapy
• Prior chemotherapy, adjuvant therapy, or radiotherapy for lung cancer, other than standard concurrent chemoradiation as described above
• Prior therapy with a PD-1, PD-L1, or CTLA-4 inhibitor or a lung cancer-specific vaccine therapy
• Presence of metastatic disease (stage IV NSCLC) is not allowed. Subjects must be evaluated with a PET scan within 28 days prior to registration for protocol therapy to exclude metastatic disease
• No active second cancers
• Evidence of active autoimmune disease requiring systemic treatment within the past 90 days or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
• Interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids
• Diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy (excludes inhaled corticosteroids) within 7 days of first dose of study drug
• History of psychiatric illness or social situations that would limit compliance with study requirements
• Clinically active infection as judged by the treating investigator (≥ Grade 2 by CTCAE v4) including known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator