| Eligibility |
Inclusion Criteria:
1. Subjects with histologically- or cytologically- documented NSCLC who present with
Stage IIIB-IV disease (according to version 7 of the International Association for the
Study of Lung Cancer Staging Manual in Thoracic Oncology), or disease recurrence or
progression following multi-modal therapy (radiation therapy, surgical resection or
radical chemo-radiotherapy in locally advanced disease).
2. Fresh cutting specimens or hollow needle aspiration specimens must be provided. A
formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of
tumor sample (must be recent) must be available for biomarker evaluation. In the case
of unstained slides, a minimum of 8 slides are necessary to conduct the planned
biomarker analyses. Specimens must be received by the central lab prior to
randomization. Biopsy should be excisional, incisional or core needle.
3. Subjects must have experienced disease recurrence or progression during or after one
prior platinum-containing doublet chemotherapy regimen for advanced or metastatic
disease:
1. Subjects who received maintenance therapy (non-progressors with platinum-based
doublet chemotherapy) and progressed are eligible.
2. Subjects who received adjuvant or neoadjuvant platinum-doublet chemotherapy
(after surgery and/or radiation therapy) and developed recurrent or metastatic
disease within 6 months of completing therapy are eligible.
3. Subjects with recurrent disease > 6 months after adjuvant or neoadjuvant platinum
based chemotherapy, who also subsequently progressed during or after a
platinum-doublet regimen given to treat the recurrence, are eligible.
4. Subjects with sensitizing EGFR mutation positive or ALK rearrangement positive, must
have experienced disease recurrence or progression during or after one prior tyrosine
kinase inhibitor regimen, who also have PD-L1 expression in tumor = 50%, are eligible.
5. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
Radiographic Tumor Assessment performed within 28 days of randomization.
6. Eastern Cooperative Oncology Arm (ECOG) performance status of = 1.
7. All baseline laboratory requirements will be assessed and should be obtained within
-14 days of randomization. Screening laboratory values must meet the following
criteria.
1. Absolute neutrophil count = 1.5 × 109/L (1500/mm3)
2. Platelets = 80× 109/L (100,000/mm3)
3. Hemoglobin = 9.0 g/dL (90 g/L)
4. Total bilirubin (TBIL) = 1.5 × upper limit of normal (ULN)
5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × upper
limit of normal(ULN); for subjects with liver metastases, ALT and AST = 5 × ULN
6. Serum creatinine =1.5 × ULN or creatinine clearance > 45 mL/minute (using
Cockcroft/Gault formula)
8. Female participants of childbearing potential must have a negative serum pregnancy
test within -7 days of randomization and must be willing to use very efficient barrier
methods of contraception or a barrier method plus a hormonal method starting with the
screening visit through 60 days (about 5 drug half-life + menstrual cycle) after the
last dose of SHR-1210. Male participants with a female partner(s) of child-bearing
potential must be willing to use very efficient barrier methods of contraception from
screening through 120 days (about 5 drug half-life + sperm depletion cycle) after the
last dose of SHR-1210.
9. Subjects must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests including completion of patient reported outcomes questionnaires and
other requirements of the study. Subjects must have signed and dated an IRB/IEC
approved written informed consent form in accordance with regulatory and institutional
guidelines. This must be obtained before the performance of any protocol related
procedures that are not part of normal subject care.
Exclusion Criteria:
1. Target Disease Exceptions
1. Subjects with active CNS metastases are excluded. Subjects are eligible if CNS
metastases are adequately treated and subjects are neurologically returned to
baseline (except for residual signs or symptoms related to the CNS treatment) for
at least 2 weeks prior to enrollment. In addition, subjects must be either off
corticosteroids, or on a stable or decreasing dose of = 10 mg daily prednisone
(or equivalent).
2. Subjects with carcinomatous meningitis.
2. Medical History and Concurrent Diseases
1. Subjects with active, known or suspected autoimmune disease. Subjects in
conditions not expected to recur in the absence of an external trigger are
permitted to enroll.
2. Subjects with a condition requiring systemic treatment with either
corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive
medications within 14 days of first administration of study treatment. Inhaled or
topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone
equivalent, are permitted in the absence of active autoimmune disease.
3. Prior therapy with immunostimulatory medications or tumor vaccines within 6
months.
4. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody
(including any other antibody or drug specifically targeting T-cell
co-stimulation or checkpoint pathways).
5. Treatment with any investigational agent within 5 half-life of the agent, before
the first administration of study treatment.
6. Subjects with a history of interstitial lung disease.
7. Subjects received lung radiation therapy within 6 months.
8. Other active malignancy requiring concurrent intervention.
9. Subjects with previous malignancies (except non-melanoma skin cancers, and the
following in situ cancers: bladder, endometrial, cervical/dysplasia) are excluded
unless a complete remission was achieved at least 5 years prior to study entry.
10. Subjects have had prior chemotherapy within 3 weeks prior to study, or have had
prior targeted small molecule therapy within 1 weeks prior to study, or have had
prior radiation therapy or surgical operation within 4 weeks prior to study, or
have had prior anti-tumor biotherapy within 3 weeks prior to study. All
toxicities attributed to prior anti-cancer therapy other than alopecia and
fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline before
administration of study drug.
11. Subjects must have recovered from the effects of major surgery or significant
traumatic injury at least 14 days before the first dose of study treatment
12. Subjects with active pulmonary tuberculosis.
13. Subjects with hemoptysis or hemorrhagic quantity per day is 2.5 ml or above
within 4 weeks prior to study.
3. Physical and Laboratory Test Findings
1. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).
2. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C
virus ribonucleic acid (HCV RNA) indicating acute or chronic infection. (HBV:
HBsAg positive and HBV DNA = 500 IU/mL ; HVC: HCV RNA positive and abnormal liver
function).
4. Allergies and Adverse Drug Reaction
1. History of severe hypersensitivity reactions to other monoclonal antibodies.
2. History of severe hypersensitivity reaction to intravenous infusion.
5. Other Exclusion Criteria Any other serious or uncontrolled medical disorder, active
infection, physical exam finding, laboratory finding, altered mental status, or
psychiatric condition that, in the opinion of the investigator, would limit a
subject's ability to comply with the study requirements, substantially increase risk
to the subject, or impact the interpretability of study results.
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