Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902)

Exclusion Criteria

• •1. Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks from day 1 of study drug (including investigational agents, chemotherapy, and antibody-based therapy).
• •2. Patients currently receiving extracranial palliative radiation within 2 weeks from day 1 of study drug.
• •3. Patients who:
• •1. Have had a major surgery or significant traumatic injury within 4 weeks from day 1 of study drug,
• •2. Have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or
• •3. Are anticipated to require major surgery during the course of the study.
• •4. Intolerance to PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents. (Intolerance: Toxicity that warrant no subsequent/further PD-1/PD-L1 therapy).
• •5. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent with the following exceptions:
• •1. Intermittent steroids (not to exceed prednisone 10 mg every day or equivalent dosing) may be used on an as-needed basis (e.g., treatment for chemotherapy- related nausea, anorexia and fatigue.)
• •2. Patients on physiologic replacement doses of steroids due to adrenal insufficiency for any reason may remain on these medications.
• •3. Topical, inhaled or intra-articular corticosteroids
• •6. Symptomatic brain or leptomeningeal metastases, including patients who continue to require glucocorticoids and/or antiseizure therapy for brain or leptomeningeal metastases.
• •1. Treated, asymptomatic metastases are permitted provided the patient has completed radiation at least 2 weeks prior to day 1 and has been off steroids for at least 2 weeks prior to day 1 of study drug.
• •2. Stable (MRI or CT with contrast performed \>4 weeks apart), untreated brain metastases are permitted if patient does not require steroids and/or antiseizure therapy is not required.
• •7. Presence of poorly controlled atrial fibrillation (ventricular heart rate \>100 bpm) by EKG.
• •8. Previous history of CVA, TIA, angina pectoris, acute MI or history of recent re-perfusion procedures (e.g., PTCA), pulmonary embolus or untreated deep vein thrombosis within 6 months from day 1 of study drug. NOTE: Subjects with recent deep vein thrombosis and/or pulmonary embolus who have been therapeutically anti-coagulated for at least 6 weeks are eligible.
• •9. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study. Examples include but are not limited to:
• •1. Active (acute or chronic) infections requiring treatment with antibiotics.
• •2. Liver disease such as cirrhosis, chronic active or persistent hepatitis B or C or HIV.
• •3. Age related macular degeneration, atypical hemolytic uremia syndrome, glomerulonephritis, or known autoimmune diseases.
• •4. A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy
• •10. History of interstitial pneumonitis of autoimmune etiology (including immune checkpoint pneumonitis) which has been symptomatic and/or required treatment. History of radiation pneumonitis is allowed if the patient has recovered and does not currently require steroid therapy.
• •11. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1 of study drug
• •12. Known autoimmune conditions requiring systemic immune suppressive therapy other than prednisone less than or equal to 10 mg.
• •13. Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS).
• •14. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. See Section 6.3.1.1 for a complete list of medically acceptable birth control methods.
• •15. Corrected QTc interval \> 480 msec. If QTc interval is \> 480 msec, then 2 additional ECGs should be obtained over a brief period (e.g., within 15-20 minutes) to confirm the abnormality. The average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the subject will be excluded from the study. The same method of QTc determination must be used throughout the subject's participation in the trial.
• •16. Patients unwilling to or unable to comply with the protocol.