Ensayos clínicos

Inclusion Criteria:

• Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluation.
• Age 18 years or older.
• Body weight ≥ 35 kg.
• Subjects must have histologically or cytologically documented NSCLC who present with locally advanced, unresectable, Stage III disease.
• Subjects must have completed, without progressing, definitive cCRT within 28 days prior to being randomized into the study: 
  • Definitive radiotherapy refers to a total dose ≥ 60 Gy at 1.8 Gy per fraction or bioequivalent dose;
  • Concurrent chemotherapy refers to a platinum-based doublet;
  • The final chemotherapy administration must end prior to, or concurrently with, the final dose of radiation.
• Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1 (RECIST v1.1 guidelines permit previously irradiated lesions to be considered measurable if defined in the protocol).
• Provision of tumor tissue sample, when available, from original diagnosis obtained before initiation of chemoradiotherapy (tumor tissue block or unstained slides are acceptable).
• Life expectancy ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 9. Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1.
• Adequate organ and marrow function as defined below:
  • Hematological
    • Hemoglobin* ≥ 9.0 g/dL (5.59 mmo1/L)
    • Absolute neutrophil count* ≥ 1.0 x 10^9 (1000 per mm^3)
    • Platelet count* ≥ 100 x 10^9 (100,000 per mm^3)
  • Hepatic
    • Total bilirubin ≤ 1.5 x ULN in the absence of Gilbert's syndrome
      • ≤ 3 x ULN if the patient has Gilbert's syndrome
    • Alanine transaminase and aspartate transaminase ≤ 2.5 x ULN
  • Renal
    • Calculated creatinine clearance**  ≥ 40 mL/minute
  • ULN = upper limit normal.
• *   Hematological criteria cannot be met with ongoing or recent blood transfusions (within 14 days prior to the scheduled first dose of study treatment) or require growth factor support (within 21 days prior to the scheduled first dose of study treatment).
• ** As determined by Cockcroft-Gault (using actual body weight; Cockcroft and Gault, 1976) or 24-hour urine creatinine clearance.
• Females of childbearing potential and non-sterilized male subjects with female partners of childbearing potential must use effective methods of contraception from screening to 180 days after the final dose of study treatment.

Exclusion Criteria:

• Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Mixed small cell and non-small cell lung cancer histology.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. The following are exceptions to this criterion: 
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection);
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent;
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
• Prior exposure to any anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody for the treatment of NSCLC .
• Any unresolved toxicity National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) > Grade 2 from the prior chemoradiation therapy.
• Subjects with history of ≥ Grade 2 pneumonitis from prior chemoradiation therapy.
• Subjects with a history of venous thrombosis within the past 3 months.
• Subjects with history of myocardial infarction, transient ischemic attack, or stroke in the past 6 months.
• Congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification.
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study drug.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Subjects with vitiligo or alopecia;
  • Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
  • Any chronic skin condition that does not require systemic therapy;
  • Subjects with celiac disease controlled by diet alone.
• History of active primary immunodeficiency.
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
• History of allogenic organ transplantation.
• Known allergy or hypersensitivity to study drug formulation(s).
• QTcF interval ≥ 470 ms.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• Receipt of live attenuated vaccination within 30 days prior to study entry.
• History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study drug and of low potential risk for recurrence;
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
  • Adequately treated carcinoma in situ without evidence of disease.
• Females who are pregnant, lactating, or intend to become pregnant during their participation in the study.