Trabedersen (OT-101) With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD-L1

The goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug OT-101/Trabedersen when combined with Pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of Non-Small Cell Lung Cancer. The main question(s) it aims to answer are:

• What medical problems to participants have when taking OT101 together with Pembrolizumab?
• What is the correct dose of OT-101 to use when evaluating the safety and efficacy of the combination therapy?
• Does the combination therapy delay progression or relapse of the participants Non-Small Cell Lung Cancer?

Participants will:

• Receive intravenous OT-101/Trabedersen for 4 days once every 2 weeks. Clinic visits are required to receive and disconnect the infusion.
• Receive intravenous Pembrolizumab once every 6 weeks.

In Phase I, dose escalation/de-escalation of OT101/Trabedersen is performed using a BOIN design to determine dose limiting toxicity (DLT) and the recommended phase 2 dose (RP2D) when combined with Pembrolizumab.

In Phase II, subjects receive the RP2D of OT101/Trabedersen together with Pembrolizumab until disease relapse, progression [as determined by immune Response Evaluation Criteria in Solid Tumours (iRECIST) criteria], or death.

Inclusion criteria

• Age ≥ 19 years
• Histologically/cytologically proven diagnosis of non-small cell lung cancer (NSCLC) with a PD-L1 of at least 1%
• Metastatic disease or disease not amenable for curative intent therapy
• No prior treatment for metastatic NSCLC. Early-stage disease therapy acceptable if completed at least six months prior and did not include immunotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Measurable disease by RECIST criteria
• Adequate organ and marrow function as defined below:

• Absolute neutrophil count ≥1,500/mm3
• Platelets ≥100,000/mm3
• Hemoglobin >9.0 mg/dL
• Creatinine clearance > 60 ml/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
• Total serum bilirubin <1.5 X upper limit of normal (ULN) except if known to have Gilbert's syndrome, then excluded if total bilirubin >2.5 X ULN
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN; if participant has liver metastases, ≤5x ULN
• For females of childbearing potential, negative serum or urine pregnancy test ≤7 days of treatment, & agree to use effective contraceptive during treatment & 90 days after end of treatment
• Male participants must agree to use effective contraception during the trial & for 90 days after end of treatment
• Able to give informed consent

Exclusion criteria

• Received any systemic treatments including investigational agents within the last 28 days
• Known hypersensitivity to any of the excipients of OT101 or pembrolizumab
• Received radiotherapy within 14 days of the study intervention. Palliative radiation is allowed during the study with a 1-week washout
• Pregnant or breast-feeding women
• History of autoimmune diseases that required systemic treatment in the past 2 years with agents such as, but not limited to, corticosteroids or immunosuppressive drugs. Thyroid replacement for hypothyroidism, insulin treatment for type I diabetes or corticosteroids adrenal/pituitary insufficiency are allowed.
• Uncontrolled systemic diseases that in the opinion of the investigator may interfere with the protocol activities
• Known active second malignancy that needs treatment. Exceptions include basal cell or squamous cancers of the skin, bladder or cervical carcinoma in situ, prostate cancer on hormone therapy alone.
• Immunodeficiency diagnosis or receiving chronic steroids that exceed a dose equivalent to prednisone 10 mg daily
• Symptomatic brain metastases. Asymptomatic metastases or having received treatment for brain metastases and are off steroid therapy is acceptable.
• Known psychiatric or substance use that would interfere with the study requirements
• Inability to co-operate with the requirements of the protocol