In this study, subjects will be randomly assigned to receive either carboplatin and
pemetrexed for 4-6 cycles followed by pemetrexed maintenance until progression or
unacceptable toxicity, OR receive SHR-1210 combined with carboplatin and pemetrexed
chemotherapy for 4-6 cycles followed by pemetrexed maintenance with SHR-1210 until
progression or unacceptable toxicity (SHR-1210 for a maximum of 2 years).
Subjects assigned to the chemotherapy arm will have the opportunity to crossover to receive
SHR-1210 monotherapy once they experience progression of disease (PD) defined by RECIST 1.1
and meet all the crossover criteria.
Inclusion Criteria:
- 1. Subjects who are chemotherapy naive and have Stage IIIB-IV non-squamous NSCLC.
- 2. Subjects should not have a previously detected sensitizing EGFR mutation or ALK
fusion oncogene.
- 3. Fresh cutting or ≤6 months preservation specimens must be provided.
- 4. No prior systemic treatment. Subjects who have received prior neo-adjuvant,
adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic
disease must have experienced a treatment free interval of at least 12 months from
randomization since the last chemotherapy cycle.
- 5. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
- 6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
- 7. Have a life expectancy of at least 3 months.
- 8. All baseline laboratory requirements will be assessed and should be obtained within
14 days prior to the first administration of study treatment.
- 9. Female Subjects of childbearing potential must have a negative serum pregnancy test
within 3 days before the first dose and must be willing to use very efficient barrier
methods of contraception for the course of the study through 180 days after the last
dose of study treatment.
- 10. Male Subjects with a female partner(s) of child-bearing potential must be willing
to use very efficient barrier methods of contraception for the course of the study
through 180 days after the last dose of study treatment.
- 11. Subjects has voluntarily agreed to participate by giving written informed
consent/assent for the trial. The subject may also provide consent/assent for Future
Biomedical Research.
Exclusion Criteria:
- 1. Target Disease Exceptions
1. Subjects with predominantly squamous cell histology NSCLC, or SCLC.
2. Subjects with epidermal growth factor receptor (EGFR)-sensitizing mutation and/or
anaplastic lymphoma kinase (ALK) translocation.
3. Subjects with no measurable disease by CT or MRI per RECIST 1.1 criteria.
4. Subjects with carcinomatous meningitis, or symptoms of spinal cord compression.
5. Subjects with active CNS metastases are excluded.
6. Subjects who can receive surgical resection or radical radiotherapy.
7. 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).
- 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, or not
requiring systemic treatment 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 systemic immunostimulatory agents within 1 months of the first
dose of trial treatment.
4. Subjects are currently participating and receiving study therapy or had
participated in a study of an investigational agent and received study therapy or
used an investigational device within 4 weeks or 5 half-value period life of the
agent, before the first dose of trial treatment.
5. Subjects who expected to require any other form of antineoplastic therapy while
on study (including maintenance therapy with another agent for NSCLC).
6. Subjects received major surgery or radiation therapy of > 30 Gy not to chest
within 4 weeks of the first dose of study treatment, or radiation therapy of > 30
Gy to chest within 24 weeks of the first dose of study treatment, or radiation
therapy of < 30 Gy to chest within 2 weeks of the first dose of study treatment,
and had not recovered from the toxicity and/or complications of the most recent
prior chemotherapy to Grade 1 or less (except alopecia or fatigue).
7. Subjects with a history of interstitial lung disease, or other disease may
interfere with the detection or treatment of suspected drug-related lung
toxicity.
8. Other active malignancy requiring concurrent intervention.
9. Subjects with previous malignancies (except non-melanoma skin cancers, and
thefollowing 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 with clinically significant cardiovascular and cerebrovascular diseases.
11. Subjects with active pulmonary tuberculosis.
12. Subjects have severe infections within 4 weeks of the first dose of study
treatment.
13. Subjects had or plan to have allogeneic bone marrow transplantation or solid
organ transplant.
14. Subjects had administration of a live, attenuated vaccine within 30 days of the
first dose of study treatment or anticipation that such a live attenuated vaccine
will be required during the study.
15. Subjects with contraindications to platinum therapy.
- 3. Physical and Laboratory Test Findings
1. Known history of testing positive for human immunodeficiency virus (HIV) or
2. known acquired immunodeficiency syndrome (AIDS).
3. Known history of active Hepatitis B or C.
4. Subjects with severe pleural effusion, pericardial effusion, or ascites need
repeated drainage.
- 4. History of severe hypersensitivity reactions to other monoclonal antibodies, or
intravenous infusion, or carboplatin, or pemetrexed.
- 5. Subjects have known psychiatric or substance abuse disorder (including
alcohol\smoking), or be regular user (including "recreational use") of any illicit
drugs that would interfere with cooperation with the requirements of the trial.
- 6. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating Investigator.
