Circulating microRNAs to choose the IO strategy in PD-L1≥50% NSCLC patients: the Ark clinical trial

Prior treatment

• Prior systemic therapy for the treatment of metastatic NSCLC. Participants who have received neoadjuvant or adjuvant chemotherapy are eligible if the neoadjuvant/adjuvant therapy was completed at least 6 months prior to the development of metastatic disease.
• Have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Presence of driver sensitizing alteration for which target therapy is available in clinical practice.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

Other illness

• Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Have a history of non-infectious pneumonitis that required steroids or has current pneumonitis.
• Have an active infection requiring systemic therapy.
• Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Have a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to Pembrolizumab and/or chemptherapy or any of their excipients.

Lab values

• Have 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.
• PD-L1 expression has been assessed as "low" by pathology laboratory (PD-L1<50%)

Other

• 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.
• Not characterized by High-MSC risk level according to central prescreening evaluation

• Diagnosis of NSCLC in stage IIIC/ IV
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• No history of active malignancy requiring treatment
• Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 15 days of treatment initiation.
• Do not have driver alterations (EGFR, ALK, ROS-1, or BRAF V600E mutation or other genomic aberration for which an approved targeted therapy is available).
• PD-L1 ≥50% tumor as determined by immunohistochemistry with anti-PD-L1 antibody (DAKO 22C3).
• Have not received prior systemic treatment for advanced NSCLC
• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥18 years of age on day of signing informed consent
• Have measurable disease based on RECIST criteria version 1.1. Measurable lesions situated in a previously irradiated area may be considered target lesions if progression has been demonstrated in such lesions.
• Have a performance status of 0-1 on the ECOG Performance Scale.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.