Clinical Trials

Inclusion Criteria:

• Subjects must provide written informed consent prior to any screening procedures being performed.
• Male and female patients ≥ 18 years of age from the date of birth.
• Histologically confirmed NSCLC stage IB-IIIA (per AJCC 8th edition), deemed suitable for primary resection by treating surgeon, except for N2 and T4 tumors.
• Subject must be eligible for surgery and with a planned surgical resection in approximately 4-6 weeks (after the first dose of study treatment).
• A mandatory newly obtained tissue biopsy from primary site is required for study enrollment. An archival biopsy is also acceptable if obtained up to 5 months before first day of study treatment and if the subject did not go through antineoplastic systemic therapies between biopsy collection date and beginning of study treatment.
  • Note: Aspirates will not be accepted.
• Subjects must have adequate organ function including the following laboratory values at the screening visit:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L;
  • Platelets ≥ 100 x 109 /L;
  • Hemoglobin (Hgb) > 9 g/dL;
  • Creatinine clearance greater than 45 mL/min by calculation using Cockcroft-Gault formula;
  • Total bilirubin (TBIL) ≤ 1.5 x upper limit of normal (ULN);
  • Aspartate transaminase (AST) ≤ 3 x ULN;
  • Alanine transaminase (ALT) ≤ 3 x ULN.
  • Serum amylase ≤ 2 x ULN or pancreatic amylase ≤ 1.5 x ULN
• Subject must have adequate cardiovacular and respiratory function to be submitted to surgical procedure as assessed per local clinical practice.
• Eastern Cooperative oncology group (ECOG) performance status of 0 or 1.
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

• Subjects with unresectable or metastatic disease.
• History of severe hypersensitivity reactions to monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
• Presence or history of a malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following:
  • completely resected basal cell and squamous cell skin cancers;
  • completely resected carcinoma in situ of any type.
• Subjects who received prior systemic therapy (including chemotherapy, other anti-cancer therapies and any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) in the past 3 years before screening
• Active autoimmune disease that has required systemic treatment in the past 2 years prior to randomization. Control of the disorder with replacement therapy is permitted.
• Uncontrolled diabetes as defined per the investigator.
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
  • Unstable angina or myocardial infarction within 6 months prior to screening;
  • History of documented congestive heart failure (CHF) (New York Heart Association functional classification III-IV);
  • Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to randomization;
  • Ventricular arrhythmias;
  • Supraventricular and nodal arrhythmias not controlled with medication;
  • Other cardiac arrhythmia not controlled with medication.
• Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to randomization or who have not recovered from side effects of such procedure. Videoassisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the study ≥ 1 week after the procedure.
• Subject with suspected or proven immunocompromised state or infections including:
  • Evidence of active or latent tuberculosis (TB) as determined by locally approved screening methods. If presence of TB (active or latent) is established then treatment for TB must have been completed according to locally approved country guidelines prior to screening for the study;
  • Chronic or active hepatitis B or C;
  • Known history of testing positive for Human Immunodeficiency Virus (HIV) infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test;
  • Any other medical condition (such as active infection, treated or untreated), which in the opinion of the investigator places the patient at an unacceptable risk for participation in immunomodulatory therapy. Subjects with localized condition unlikely to lead to a systemic infection; e.g., chronic nail fungal infection are eligible;
  • Allogeneic bone marrow or solid organ transplant;
  • Subject receiving any biologic drugs targeting the immune system (for example, TNFα blockers, anakinra, rituximab, abatacept, or tocilizumab);
  • Current treatment with any immune modulating agent in doses with systemic effects; e.g.,
  • Current systemic glucocorticoid therapy except for daily glucocorticoidreplacement for conditions such as adrenal or pituitary insufficiency and topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted;
  • Prednisone > 20 mg (or equivalent) daily for > 14 days;
  • Prednisone > 5 mg and ≤ 20 mg (or equivalent) daily for > 30 days;
  • Equivalent dose of methotrexate > 15 mg weekly.
• Live vaccination within 3 months prior to randomization.
• Subjects who have received an investigational drug or device within 5 half-lives prior to randomization or those who are expected to participate in any other investigational drug or device during the conduct of the study.
• Pregnant or breast-feeding (lactating) women, or women who plan to become pregnant or breast-feed during the study, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during the study and for 4 months after stopping study treatment.
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception).
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
• Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.
• Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception, women should have been stabilized on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or bilateral tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
• Subject has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate subject participation in the clinical study, or compromise compliance with the protocol (e.g., chronic pancreatitis, uncontrolled diabetes mellitus.

Eligibility last updated 9/7/21. Questions regarding updates should be directed to the study team contact.