SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody. This is a randomized,Phase III, multicenter ,open-label study designed to evaluate the safety and efficacy of SHR-1210 with carboplatin and pemetrexed versus carboplatin-pemetrexed in subjects who are chemotherapy naive and have Stage IIIB/IV non-squamous NSCLC. The primary hypothesis is that SHR-1210 combined with carboplatin and pemetrexed prolongs Progression Free Survival (PFS) in per RECIST 1.1 by blinded independent central review (ITT population and population was indicated by high PD-L1 expression) compared to carboplatin and pemetrexed treatment .
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
419
SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody.
Carboplatin
Pemetrexed
Tongji University, Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, China
Progression-Free Survival in the intent-to-treat (ITT) population
PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.
Time frame: up to 24 months
Progression-Free Survival in the PD-L1-selected population
PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.
Time frame: up to 24 months
Overall Response Rate (ORR)
Determined using RECIST v1.1 criteria
Time frame: up to 24 months
Duration of Response Rate(DoR)
Determined using RECIST v1.1 criteria
Time frame: up to 24 months
Time To Progression (TTP)
Determined using RECIST v1.1 criteria
Time frame: up to 24 months
Disease Control Rate (DCR)
Determined using RECIST v1.1 criteria
Time frame: up to 24 months
Overall Survival
Defined as the time from randomization to death from any cause.
Time frame: up to 24 months
Number of Subjects with treatment-related adverse events (AEs)
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
Time frame: up to 24 months
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