A Phase III, Randomized, Open-Label, Multi-center Study of SHR-1210(Anti-PD-1 Antibody) in Combination With Pemetrexed and Carboplatin as First Line Therapy in Subjects With Advanced/Metastatic Non-squamous Non-small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- SHR-1210
- Conditions
- Lung Neoplasms
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 419
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival in the intent-to-treat (ITT) population
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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 .
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who are chemotherapy naive and have Stage IIIB-IV non-squamous NSCLC.
- •Subjects should not have a previously detected sensitizing EGFR mutation or ALK fusion oncogene.
- •Fresh cutting or ≤6 months preservation specimens must be provided.
- •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.
- •Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Have a life expectancy of at least 3 months.
- •All baseline laboratory requirements will be assessed and should be obtained within 14 days prior to the first administration of study treatment.
- •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.
- •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.
Exclusion Criteria
- •Target Disease Exceptions
- •Subjects with predominantly squamous cell histology NSCLC, or SCLC.
- •Subjects with epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation.
- •Subjects with no measurable disease by CT or MRI per RECIST 1.1 criteria.
- •Subjects with carcinomatous meningitis, or symptoms of spinal cord compression.
- •Subjects with active CNS metastases are excluded.
- •Subjects who can receive surgical resection or radical radiotherapy.
- •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).
- •Medical History and Concurrent Diseases
- •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.
Arms & Interventions
SHR-1210+Chemotherapy
Subjects receive SHR-1210 200mg and pemetrexed 500 mg/m\^2 and carboplatin AUC 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional SHR-1210 200mg and pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.
Intervention: SHR-1210
SHR-1210+Chemotherapy
Subjects receive SHR-1210 200mg and pemetrexed 500 mg/m\^2 and carboplatin AUC 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional SHR-1210 200mg and pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.
Intervention: Carboplatin
SHR-1210+Chemotherapy
Subjects receive SHR-1210 200mg and pemetrexed 500 mg/m\^2 and carboplatin AUC 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional SHR-1210 200mg and pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.
Intervention: Pemetrexed
Chemotherapy
Subjects receive pemetrexed 500 mg/m\^2 and carboplatin Area Under the Curve (AUC) 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD. If PD occurs, Subjects may be able to receive SHR-1210 Q3W for the remainder of the study or until documented PD.
Intervention: Carboplatin
Chemotherapy
Subjects receive pemetrexed 500 mg/m\^2 and carboplatin Area Under the Curve (AUC) 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD. If PD occurs, Subjects may be able to receive SHR-1210 Q3W for the remainder of the study or until documented PD.
Intervention: Pemetrexed
Outcomes
Primary Outcomes
Progression-Free Survival in the intent-to-treat (ITT) population
Time Frame: up to 24 months
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.
Progression-Free Survival in the PD-L1-selected population
Time Frame: up to 24 months
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.
Secondary Outcomes
- Overall Survival(up to 24 months)
- Number of Subjects with treatment-related adverse events (AEs)(up to 24 months)
- Overall Response Rate (ORR)(up to 24 months)
- Duration of Response Rate(DoR)(up to 24 months)
- Time To Progression (TTP)(up to 24 months)
- Disease Control Rate (DCR)(up to 24 months)