An Open-label, Single-arm, Multi-center, Phase 2 Study to Evaluate SHR-1210(Anti-PD-1 Antibody) in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Lung Neoplasms
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 146
- Locations
- 1
- Primary Endpoint
- Objective response rate
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is an open-label, single-arm, multi-center, phase 2 Study to evaluate SHR-1210(anti-PD-1 antibody) in in adult Chinese patients with advanced or metastatic non-small cell lung cancer who failed or progressed to prior first-line systemic treatment.
Enrolled subjects will be assigned to 4 cohorts on the basis of PD-L1 expression in tumor cells(<1%, ≥1%-25%, ≥25%-50%, ≥50%) all will be treated with the standard SHR-1210 dose (200mg) , Q2W, until documented progressive disease (PD) occurs. Subjects will return to the clinic once every two weeks. Radiographic disease assessments will be performed every 6 weeks.
The primary study hypothesis is that treatment with SHR-1210 improves Objective Response Rate when compare with standard second-line therapy, no matter how much PD-L1 expression in tumor.
Detailed Description
In similar clinical trials, anti-PD-1 and anti-PD-L1 antibodies produce durable responses in approximately 20% of unselected patients with advanced non-small-cell lung cancer. Developing reliable, validated biomarkers that identify patients with an increased probability of response to these antibodies remains a challenge. Because the PD-1 pathway may be a key mechanism of immune escape in a subgroup of patients with non-small-cell lung cancer, PD-L1 expression in tumor or inflammatory cells is a candidate biomarker. However, PD-L1 expression has not been formally validated as a biomarker in contemporaneously collected tumor tissue. Additionally the purpose of the study is to assess the correlation between the expression of PD-L1 in the tumor and the response to treatment with SHR-1210 in non-small cell lung cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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).
- •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.
- •Subjects must have experienced disease recurrence or progression during or after one prior platinum-containing doublet chemotherapy regimen for advanced or metastatic disease:
- •Subjects who received maintenance therapy (non-progressors with platinum-based doublet chemotherapy) and progressed are eligible.
- •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.
- •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.
- •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.
- •Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria; Radiographic Tumor Assessment performed within 28 days of randomization.
- •Eastern Cooperative Oncology Arm (ECOG) performance status of ≤
- •All baseline laboratory requirements will be assessed and should be obtained within -14 days of randomization. Screening laboratory values must meet the following criteria.
Exclusion Criteria
- •Target Disease Exceptions
- •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).
- •Subjects with carcinomatous meningitis.
- •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 are permitted to enroll.
- •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.
- •Prior therapy with immunostimulatory medications or tumor vaccines within 6 months.
- •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).
- •Treatment with any investigational agent within 5 half-life of the agent, before the first administration of study treatment.
- •Subjects with a history of interstitial lung disease.
Outcomes
Primary Outcomes
Objective response rate
Time Frame: Determined using RECIST v1.1 criteria, up to approximately 1 year
Objective response is defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
Secondary Outcomes
- Progression-Free Survival(Determined using RECIST v1.1 criteria, up to approximately 1 year)
- Duration of Response Rate(Determined using RECIST v1.1 criteria, up to approximately 1 year)
- Overall Survival Rate at 12-month(up to approximately 1 year)
- Number of participants with treatment-related adverse events (AEs)(up to approximately 1 year)