The purpose of this research study is to determine the maximum tolerated dose of GT103 and
investigate the safety and effectiveness of the study drug.
This is a Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage
(III/IV) and Recurrent Non-Small Cell Lung Cancer.
Patients with histologically confirmed recurrent, advanced stage of lung cancer, and there
are no other standard therapies available may be eligible to participate in this study.
- Histologically and/or cytologically confirmed advanced stage III, IV or recurrent
NSCLC that is refractory to immunotherapy (anti-PD-1/PD-L1) and a platinum-based
chemotherapy, either concomitantly or sequentially. Patients with EGFR, ALK, or ROS1
alterations must have received at least one prior TKI and prior chemotherapy (at least
one platinum doublet regimen).
- Disease must be measurable by RECIST 1.1 criteria (see Appendix A). Tumor lesions in a
previously irradiated area are considered measurable IF progression has been
demonstrated in such lesions after radiation.
- Age ≥ 18 years
- ECOG Performance Status 0 or 1 (see Appendix B) 5. Adequate bone marrow function as
- ANC ≥ 1.5 x 109 o Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL; Erythropoietin and transfusion support is permitted. If
patient is receiving supportive care, hemoglobin must be stable above or equal to
9 g/dL for at least 2 weeks prior to day 1 of study drug without blood
transfusion to maintain hemoglobin level.
- Adequate liver function as shown by:
- serum bilirubin ≤ 1.5x ULN
- ALT and AST ≤ 2.5x ULN ; ≤ 5 x ULN with liver metastasis
- Adequate renal function: defined as serum creatinine ≤1.5 x ULN OR creatinine
clearance (estimated) ≥ 50 cc/min by Cockroft Gault or 24-hour urine (see Appendix E).
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at
screening and prior to treatment on Cycle 1 Day 1; both men and women must be willing
to use two medically accepted methods of contraception, one of them being a barrier
method during the study and for 6 months after last study drug administration. See
Section 220.127.116.11 for a list of acceptable methods of contraception. -
- Signed informed consent
- Willing and able to comply with clinic visits and study-related procedures and
- 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).
- Patients currently receiving extracranial palliative radiation within 2 weeks from day
1 of study drug.
- 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.
- Intolerance to PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically
targeting Tcell co-stimulation or immune checkpoint pathways, including prior therapy
with anti-tumor vaccines or other immune-stimulatory anti- tumor agents.
- 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
- Symptomatic brain or leptomeningeal metastases, including patients who continue to
require glucocorticoids and/or antiseizure therapy for brain or leptomeningeal
metastases. 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. 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.
- Severe chronic obstructive or other pulmonary disease with hypoxemia (requires
supplementary oxygen, or in the opinion of the investigator any physiological state
likely to cause systemic or regional hypoxemia).
- Presence of poorly controlled atrial fibrillation (ventricular heart rate >100 bpm) by
- 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 who have been therapeutically anti-coagulated for at least 6 weeks are
- 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
3. Age related macular degeneration, atypical hemolytic uremia syndrome,
glomerulonephritis, or known autoimmune diseases.
- History of interstitial pneumonitis from any cause
- 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
- Known autoimmune conditions requiring systemic immune suppressive therapy other than
prednisone less than or equal to 10 mg.
- Known history of HIV seropositivity or known acquired immunodeficiency syndrome
- Female patients who are pregnant or breast feeding, or adults of reproductive
potential who are not using effective birth control methods. See Section 18.104.22.168 for a
complete list of medically acceptable birth control methods.
- 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.
- Patients unwilling to or unable to comply with the protocol.