| Eligibility |
Inclusion Criteria;
1. Histologically and/or cytologically confirmed advanced stage III, IV or recurrent
NSCLC whose tumors have progressed on prior therapy.
2. Prior Therapy:
- Patients must have received immunotherapy (anti-PD-1/PD-Ll) and a platinum- based
chemotherapy either concomitantly or sequentially. There is no defined window of
time since receiving immunotherapy. Immunotherapy does not have to be the
immediate treatment prior to this protocol therapy.
- Patients with EGFR, ALK, or ROS1 alterations must have received at least one
prior TKI and prior chemotherapy (at least one platinum doublet regimen).
- Stage III patients:
If previously treated with immunotherapy participants with investigator-assessed
radiographic disease progression or recurrence in less than 6 months after the last
dose of immunotherapy in Stage III B/C disease post concurrent chemoradiotherapy
followed by immunotherapy are eligible. Radiographic progression must be documented
via pretreatment scan as compared to the prior therapy baseline scan in order for the
participant to be eligible.
3. 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.
4. Age = 18 years
5. ECOG Performance Status 0 or 1 (see Appendix B)
6. Adequate bone marrow function as shown by:
- ANC = 1.5 x 109
- 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.
7. Adequate liver function as shown by:
- serum bilirubin = 1.5x ULN
- ALT and AST = 2.5x ULN ; = 5 x ULN with liver metastasis
8. Adequate renal function: defined as creatinine clearance (estimated) = 50 cc/min by
Cockroft Gault or 24-hour urine (see Appendix E).
9. 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 6.3.1.1 for a list of acceptable methods of contraception.
10. Signed informed consent
11. Willing and able to comply with clinic visits and study-related procedures and
requirements.
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.
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