| Eligibility |
Inclusion Criteria:
1. Male or female, age = 18 years.
2. Histologically or cytologically confirmed diagnosis of unresectable locally advanced
or metastatic (stage IIIB-IV) NSCLC.
3. Previously treated with a PD-1 inhibitor, alone or in combination with another
systemic therapy, and have unequivocal progressive disease confirmed by imaging or
pathology. The PD-1 inhibitor must be the products already in the market.
4. Previously received at least 2 systemic chemotherapy regimens (containing platinum is
required).
5. Tumor tissue can be provided for research.
6. ECOG performance status of 0 or 1.
7. Have at least one measurable target lesion as defined by RECIST v.1.1.
8. The following laboratory results within 7 days prior to study drug administration:
Hemoglobin =90g/L independent of transfusion, Neutrophils =1.5×109/L, Platelets
=90×109/L, Creatinine =1.5×ULN, Bilirubin =1.5×ULN (unless known Gilbert's disease
where it must be =3×ULN), AST and ALT =2.5×ULN (unless known hepatic metastasis where
it must be =5×ULN); INR=1.5×ULN, PT and aPTT =1.5×ULN.
9. Life expectancy =12 weeks.
10. Have the ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
1. Prior use of a PDL1 or PDL2, anti-CTLA4 antibody or any other antibody or drug that
specifically targets immune checkpoint pathway.
2. Prior use of HDAC inhibitor.
3. Known history of intolerance to PD-1 inhibitor treatment.
4. Known driver genes mutation (EGFR, ALK, ROS1 or RET).
5. Use of any anti-tumor therapy or investigational agent and device within 28 days
before the first dose of study drug; or received thoracic radiation >30Gy within 6
months before the first dose.
6. Use of systemic immunosuppressive therapy within 28 days before the first dose of
study drug. Inhaled or topical steroids and physiological dose of systemic
glucocorticoid (=10 mg daily prednisone equivalents) are permitted.
7. Received a live vaccine within 28 days before the first dose of study drug or planned
to receive during the study period. Note: Seasonal influenza vaccines for injection
are generally inactivated flu vaccines and are allowed; and COVID-19 vaccine also are
allowed.
8. Received major surgery (craniotomy, thoracotomy or laparotomy) within 28 days before
the first dose of study drug, or there are still serious and unhealed wounds, ulcers
or fractures judged by the investigator during the screening period.
9. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation.
10. Before the first dose of study drug, subjects who has not recovered ( = Grade 1
defined by CTCAE V5.0) from AEs due to prior anti-cancer therapy. Except for hair
loss, or laboratory test abnormalities assessed by the investigator as clinically
insignificant.
11. Subjects with obvious clinical symptoms or need drainage of pleural effusion, ascites
and pericardial effusion, or who received drainage for the purpose of treatment within
1 month before the first dose of study drug.
12. Active autoimmune disease that has required systemic treatment in past 2 years (i.e.,
corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and are allowed.
13. Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
Previously treated brain metastases may be an exception if stable and specific other
criteria are met.
14. Uncontrollable or major cardiovascular and cerebrovascular diseases, including, but
not limited to:
1)Congestive heart failure (New York Heart Association Grade II or above); unstable angina
or myocardial infarction within the previous 6 months; or cardiac arrhythmia requiring
treatment; or left ventricular ejection fraction (LVEF)<50%; 2)Primary cardiomyopathy
(e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right
ventricular cardiomyopathy, restrictive cardiomyopathy, amorphous cardiomyopathy);
3)History of clinically significant QTcF interval prolongation, or a QTcF interval > 470
msec(female) or > 470 msec(male) during the screening period.
4)Symptomatic coronary heart disease requiring medical management during the screening
period.
5)Cerebrovascular accidents (i.e., cerebral hemorrhage, cerebral infarction, transient
ischemic attack) within the previous 6 months; 15.Active bleeding with significant clinical
significance within the previous 2 months; or subject who is taking anticoagulants, or
subject with clear high-risk bleeding tendency during the screening period.
16.Suspected interstitial lung disease (ILD) or pulmonary fibrosis or pulmonary
inflammation requiring treatment; or history of lung disease treated with oral or
intravenous steroids within the previous 6 months; or immune-related pneumonia after
previous treatment with PD-1 inhibitors.
17.Obvious gastrointestinal abnormalities during the screening period, which may affect the
intake, transport or absorption of drugs; or history of gastrointestinal perforation and /
or fistula; or history of peptic ulcer within the previous 6 months or intestinal
obstruction within the previous 3 months.
18.Urinary protein = 2+ and quantitative urinary protein = 1g/24 h during the screening
period; 19.Known active pulmonary tuberculosis, or subject who is receiving antituberculous
treatment or having received antituberculous treatment within the previous 1 years.
20.Active infection requiring intravenous therapy; or severe infection within 28 days
before the first dose of study drug.
21.Active hepatitis B (HBsAg and HBV DNA positive), or hepatitis C (HCV antibody test and
HCV RNA positive); known HIV positive or history of AIDS or other serious infectious
diseases.
22.History of pulmonary embolism within the previous 6 months or deep venous thrombosis or
any other serious venous thromboembolic event within the previous 3 months.
23.History of second malignancy, except for carcinoma in situ with adequate treatment and
no evidence of disease recurrence, non-melanomatous skin cancer or lentiginous melanoma,
completely relieved for at least 2 years before the first dose of study drug and estimated
that no other treatment is required during the study period.
24.Contraindications to any of the study drug ingredients. 25.History of hypersensitivity
to monoclonal antibody, Chidamide, study drug, or any of its excipients.
26.History of alcohol or drug abuse. 27.Unwilling or unable to comply with procedures
required in this protocol. 28.Pregnant or breast-feeding women. 29.Women of childbearing
age or spouses of male patients who are unwilling or unable to use effective methods for
contraception during the whole treatment period of this trial and within 12 weeks after the
last use of Chidamide or within 150 days after the last use of Envafolimab (whichever is
the latest).
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