An Autologous NK/CIK Cell Product (PB101) in Combination With EGFR-TKI for Treating Lung Cancer

Prior treatment

• Patients who have had radiation to the lung fields within four weeks of starting treatment. For all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting to treatment.
• Patients who have had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within two weeks prior to starting study drug or who have not recovered from side effects of such procedure. Video-assisted 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.
• Patients with a second, clinically active, cancer. Patients with second cancers which have been treated with curative intent and/or are currently inactive are allowed.
• Participants who are receiving any other investigational agents. Patients previously treated with investigational agents must complete a washout period of at least one week or five half-lives, whichever is longer, before starting treatment.
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use, except those on topical or inhaled steroids, or steroids given via local injection.

Other illness

• Patients with history of clinically significant interstitial lung disease or radiation pneumonitis.
• Patients with brain metastasis or leptomeningeal disease.
• Known history of human immunodeficiency virus (HIV) seropositivity.
• Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management.
• Active hepatitis B or C without treatment.

Lab values

• Patients with clinically significant, uncontrolled cardiovascular disease, such as: unstable angina or myocardial infarction within 6 months prior to screening, abnormal left ventricular ejection fraction (LVEF \<50%), cardiac arrhythmia not controlled with medication, uncontrolled hypertension defined as a SBP ≥ 160mm Hg and/or DBP ≥ 100mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.

Other

• Pregnancy and lactating women.
• Other situations the investigators think not eligible for participation in the research.

• Men and women 20 years of age or older.
• Subjects with histologically or cytologically confirmed stage IIIB/IV non-small cell lung cancer, not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/IASLC 7th edition proposed staging criteria.
• EGFR sensitizing mutation must be detected in tumor tissue. Specifically, patients harboring the most common mutations, deletions in exon 19 or the L858R mutation in exon 21 are eligible. Other EGFR sensitizing mutations may be eligible after discussion with the principal investigator.
• Subjects must have measurable or evaluable disease according to RECIST v1.1.
• Patients may have had a prior EGFR-TKI including gefitinib, erlotinib, afatinib, or osimertinib in the metastatic setting, but treatment duration must have been less than three months at the time of enrollment.
• Patients may have had no more than one prior line of chemotherapy or immunotherapy in the metastatic setting. At least 14 days must have elapsed from the last chemo/immunotherapy administration until the start of protocol treatment, and patients must have recovered from the side effects of any of these agents.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Acceptable organ function, as evidenced by the following laboratory data:
  • . Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x upper limit of normal (ULN). (for patients with known hepatic metastases, AST and/or ALT \<5x ULN)
  • . Total serum bilirubin ≤1.5 x ULN
  • . Absolute neutrophil count (ANC) ≥1500 cells/mm3
  • . Platelet count ≥75,000 cells/mm3
  • . Hgb ≥ 10.0 g/dL
  • . Serum creatinine levels ≤1.5 \* ULN, or calculated (by Cockcroft-Gault formula or other accepted formula) or measure creatinine clearance ≥50 mL/min.